Advertisement

Noted This Week - Archive 2021

Noted This Week - 2021 Archive

Archive of cancer-related news briefs, by week, for 2021

October 2021

October 8–14

  • The FDA authorized the marketing of the first electronic cigarette through its scientific premarket evaluation program: R.J. Reynolds's Vuse Solo device and its accompanying tobacco-flavored e-liquid pods and replacement cartridges. The agency determined that participants in a study who used only the authorized products were exposed to fewer harmful aerosols/chemicals than users of combustible cigarettes. The FDA also determined that the potential benefit to smokers who switch completely or significantly reduce their cigarette use would outweigh the risk to youth.
  • Eli Lilly announced the approval of abemaciclib (Verzenio) with endocrine therapy to treat certain early breast cancers at a high risk of recurrence. Efficacy was evaluated in the monarchE study, which included men and women with HR-positive, HER2-negative, node-positive disease who received either abemaciclib plus physician’s choice of standard endocrine therapy or standard endocrine therapy alone. Patients who received the combination therapy had a statistically significant improvement in invasive disease-free survival compared with endocrine therapy alone—86.1% vs. 79%, respectively. Overall survival data were not mature at the time of analysis.
  • Merck announced the approval of its PD-1 inhibitor pembrolizumab (Keytruda; Merck) for yet another indication—this time in combination with chemotherapy, with or without bevacizumab, for women with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1. In the KEYNOTE-826 trial, patients received either the pembrolizumab combination or placebo plus chemotherapy, with or without bevacizumab. For tumors expressing PD-L1, median overall survival was not reached in the pembrolizumab arm and was 16.3 months in the placebo arm. Median progression-free survival was 10.4 months and 8.2 months, respectively.
  • The FDA has removed a full clinical hold on studies of rusfertide (PTG-300; Protagonist Therapeutics), an injectable hepcidin mimetic under investigation in phase II trials of polycythemia vera and other blood-related medical conditions. The hold was triggered by a nonclinical finding in a transgenic mouse model indicating benign and malignant subcutaneous skin tumors, which prompted a review of four cancer cases across all rusfertide clinical trials, which involved 160 patients. Protagonist had provided the FDA with clinical safety resorts, updated consent forms, added new safety rules in study protocols, and taken other measures.

Earlier This Year:

 ::  January  ::  February  ::  March  ::  April  ::  May  ::  June  ::  July  ::  August  ::  September

Noted This Week Archive:

 ::  2021  ::  2020  ::  2019  ::  2018  ::  2017  ::  2016  ::  2015  ::  2014  ::  2013  ::  2012  ::  2011

  • In a study presented at the virtual Molecular Targets and Cancer Therapeutics Conference, the ATR inhibitor RP-3500 (Repare Therapeutics) demonstrated early clinical benefit as a single agent in cancers harboring synthetic lethal genomic alterations in DNA damage repair pathways. Notably, preliminary antitumor efficacy was seen in patients with advanced solid tumors—including ovarian, prostate, and breast cancers—that were resistant, refractory, or intolerant to standard therapies, such as PARP inhibitors. Across a variety of gene alterations, 34 of 69 evaluable patients achieved meaningful clinical benefit: 12 patients experienced an objective response, 14 patients had stable disease for at least 16 weeks, and eight patients had significant decreases in tumor markers and tumor shrinkage.
  • The American Association for Cancer Research released its 11th annual Cancer Progress Report, which underscores how cancer research, largely through federal investments in the NIH and NCI, continues to drive progress against cancer. The report chronicles advances in basic, translational, and clinical cancer research; profiles patients who have benefited from recently approved anticancer therapeutics; provides the latest information on cancer prevention, detection, and health disparities; and outlines policy recommendations. The report is available at www.cancerprogressreport.org.

October 1–7

  • Amgen released preliminary safety and efficacy data for the KRASG12C inhibitor sotorasib (Lumakras), which is being tested in 10 different combination regimens in patients with KRASG12C-mutated cancers. Results from two combination arms, one with the pan-ERBB tyrosine kinase inhibitor afatinib (Gilotrif; Boehringer Ingelheim) and the other with the MAPK inhibitor trametinib (Mekinist; Novartis), indicate no significant safety signals with either combination, and 67% to 87% of patients achieved disease control depending on the drug combination and whether they had been treated with sotorasib as monotherapy before. The results will be presented at the AACR-NCI-EORTC 2021 Molecular Targets and Cancer Therapeutics conference on October 9th.
  • A portion of Memorial Sloan-Kettering’s Oncology Knowledge Base (OncoKB) database of molecular tumor data achieved FDA recognition as a source of clinically significant and potentially clinically significant biomarkers. The database contains information about genetic alterations in 682 cancer-associated genes in 125 cancer types. Developers of tumor profiling tests can now use the "FDA-recognized alterations" on OncoKB to support premarket submissions.
  • Thermo Fisher is being sued by the estate of Henrietta Lacks over the continued sale of HeLa cells, a cell line made from Lacks’s cervical cancer without her consent in 1951. The lawsuit alleges that the company continues to profit from HeLa cells without the family’s consent or financial compensation. The estate is seeking the full amount of net profit gained by Thermo Fisher’s commercialization of the cell line.
  • NRG Oncology announced the launch of a trial to determine the best colonoscopy screening protocol for preventing colorectal cancer in people who have previously had polyps detected. The FORTE trial will evaluate whether these patients should have a repeat colonoscopy 10 years later, or after 5 and 10 years. Reseachers aim to recruit 9,500 individuals.
  • The cost of care for the 15 most common cancer types in the United States was $156.2 billion in 2018 (JAMA Netw Open 2021;4:e2127784). By studying a database of information with 402,114 privately insured patients with cancer under age 65, and 38.4 million procedures, researchers at Pennsylvania State College of Medicine in University Park found that medication costs were the largest expense, with breast cancer being the most expensive cancer type overall, totaling $3.4 billion.
  • Maintaining physical activity before and during chemotherapy is associated with better cognitive function in patients with breast cancer (J Clin Oncol 2021;39:3283–92). The prospective study, which involved 580 patients and 363 healthy age-matched controls, found that patients who remained physically active had better cognitive function immediately and 6 months post-chemotherapy.
  • Black patients with non–small cell lung cancer (NSCLC) have a 15% lower risk of death than whites when treated with immunotherapy, according to research presented at the 14th American Association for Cancer Research Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved. Using data from the 2016 National Cancer Database, investigators came to this conclusion after looking at how 3,068 patients with advanced NSCLC fared. Black patients typically have shorter survival than whites with NSCLC and are more likely to be diagnosed at a later stage, but the study shows that when Black patients have access to immunotherapy, survival disparities shrink.
  • A parent who alleged her son's cancer was caused by Bayer’s Roundup weed killer has lost her legal battle against the company. The lawsuit claimed that her child developed Burkitt lymphoma due to the glyphosate found in the weed killer, which she had used outside the family's home. However, the jury ruled in Bayer's favor, concluding that there was insufficient evidence that the chemical caused the cancer.

September 2021

September 24–30

  • David Baltimore, PhD, of the California Institute of Technology in Pasedena, was awarded the 2021 Lasker-Koshland Award for Special Achievement in Medical Science. Baltimore is credited with several fundamental discoveries spanning virology, immunology, and cancer and was jointly awarded the 1975 Nobel Prize in Physiology or Medicine for the discovery of reverse transcription. His lab also discovered the transcription factor NFκB, made advances in the understanding of BCR–ABL, and, more recently, elucidated roles of microRNAs in immune system regulation.
  • A third dose of the BNT162b2 COVID-19 vaccine (Comirnaty; Pfizer/BioNTech) substantially boosted levels of neutralizing antibodies in 80% of patients with cancer receiving active cytotoxic therapy (Nat Med 2021 Sep 30 [Epub ahead of print]). Some patients with cancer on active treatment have shown reduced antibody responses to two-shot vaccine regimens. In this study, patients with solid tumors demonstrated a median threefold increase in antibody responses after a booster shot, with no significant adverse events reported.
  • GlaxoSmithKline and Merck KGaA ended their $4 billion collaboration on bintrafusp alfa (M7824), a first-in-class drug designed to target TGFβ and PD-L1. However, the agent yielded underwhelming results in the INTR@PID Lung 07 trial, which involved patients with advanced non–small cell lung cancer. The trial was terminated early after a review by the Independent Data Monitoring Committee suggested it was unlikely to meet its primary endpoint; bintrafusp alfa also failed to show a benefit in metastatic biliary tract cancer.
  • Ziopharm Oncology recently laid off half of its workforce, eliminating 60 jobs. According to the company, the cuts were made as part of a restructuring following unforeseen delays and insufficient resources at its contract manufacturer. A clinical trial of one of Ziopharm’s chimeric antigen receptor T-cell products is now expected to start next year instead of this fall.
  • Clinical trial enrollment in the UK has dropped significantly due to the COVID-19 pandemic, according to a report from the Association of the British Pharmaceutical Industry. Although the UK initiated the most COVID-19 clinical trials of any country in Europe in 2020, non-COVID clinical trials were frequently paused early in the pandemic and are still experiencing delays and disruption. Enrollment in cancer clinical trials in the UK was down 88% in May 2020 compared with May 2019 and is recovering more slowly than in many other European countries.
  • The University of Texas MD Anderson Cancer Center in Houston and the Rare Cancer Research Foundation announced a collaboration to accelerate treatment development for rare cancers. The initiative will use the foundation’s online engagement platform to enable patients from across the United States to donate tissue samples for analysis and research projects at MD Anderson.
  • More than 2 million middle and high school students currently use electronic cigarettes (e-cigarettes), according to the FDA’s 2021 National Youth Tobacco Survey. Of those surveyed, 85% used flavored e-cigarettes, with fruit, candy, and dessert flavorings being the most popular choices. In addition, more than 25% of high school students reported using the devices daily.

September 17–23

  • Presented at the European Society of Medical Oncology Congress 2021, two studies found that adding abiraterone acetate and prednisolone (AAP) to standard treatment with androgen deprivation therapy and docetaxel for hormone-sensitive prostate cancer lengthens survival compared with standard therapy alone. In PEACE-1, men with high-burden metastatic disease who received the AAP combination lived about 2.5 years longer without disease progression—and 18 months longer overall—than those who received standard care. The STAMPEDE trial found that after 6 years, men at high risk of developing metastatic disease who received the AAP combination for 2 years had an improvement in metastasis-free survival from 69% to 82%, and an improvement in overall survival from 77% to 86%.
  • Incyte announced that the FDA approved ruxolitinib (Jakafi) for chronic graft-versus-host disease (GVHD) in patients age 12 and older after one or two other therapies fail. The approval was based on the 329-patient, phase III REACH3 study comparing ruxolitinib to best available therapy (BAT) to treat chronic GVDH following allogeneic stem cell transplantation (N Engl J Med 2021;385:228–38). After 24 weeks, the overall response rate (ORR) was 49.7% for ruxolitinib compared with 25.6% for BAT. The median duration of response was 4.2 months and 2.1 months, respectively.
  • The FDA approved cabozantinib (Cabometyx; Exelixis) for patients age 12 and older with locally advanced or metastatic differentiated thyroid cancer that has progressed following VEGFR-targeted therapy and who are ineligible for or refractory to radioactive iodine. The decision was based on the COSMIC-311 trial, in which patients received either cabozantinib or placebo with best supportive care. Median progression-free survival was 11 months for those who received cabozantinib compared with 1.9 months for those who received placebo. The ORR was 18% and 0%, respectively.
  • In addition, the agency authorized the marketing of software to assist pathologists in detecting prostate cancer. Paige Prostate is the first artificial intelligence–based software designed to identify areas on biopsy images that could be cancerous and flag them for review. In a clinical study, 16 pathologists examined 527 prostate images—171 of which showed cancer—with and without Paige Prostate. On average, the software improved pathologists’ detection of cancer by 7.3% compared with pathologists’ analyses alone.
  • A Delaware Chancery Court judge ruled that Takeda breached an agreement with AbbVie for failing to fulfill orders for the prostate cancer agent leuprolide (Lupron), maintain common good manufacturing practices, and keep a backup supply of the drug to prevent shortages. Takeda, the global supplier of the hormone therapy, manufactures it at a plant in Japan, but the company and the FDA discovered poor equipment maintenance, shortfalls in quality, and other problems at the plant in 2019 that have led to a short supply worldwide. A second trial will determine compensation for AbbVie’s lost sales.
  • New York, NY’s Memorial Sloan Kettering Cancer Center announced the establishment of a center focused on patients ages 15 to 39, a group that often faces special treatment and psychosocial needs. The Lisa and Scott Stuart Center for Adolescent and Young Adult Cancers will address underrepresentation of these patients in clinical trials; offer family planning and fertility services; tailor treatment to tumor biology, which could differ from older and younger patients; and make use of apps and social media.

September 10–16

  • The FDA granted accelerated approval to mobocertinib (Exkivity; Takeda) for patients with locally advanced or metastatic non–small cell lung cancer and EGFR exon 20 insertion mutations who have already received platinum-based chemotherapy. The approval was based on the phase I/II Study 101 trial, in which 28% of patients responded to the agent, with responses lasting a median of 17.5 months. The approval is the first for mobocertinib, a tyrosine kinase inhibitor.
  • The agency also granted accelerated approval to zanubrutinib (Brukinsa; BeiGene) for patients with relapsed/refractory marginal zone lymphoma who have received at least one anti-CD20 therapy. The decision was based on the phase II MAGNOLIA trial and the phase I/II BGB-3111-AU-003 trial, in which patients had overall response rates of 56% and 80%, respectively. Zanubrutinib is a Bruton tyrosine kinase inhibitor previously approved for mantle cell lymphoma and Waldenström macroglobulinemia.
  • Survey results presented at the International Association for the Study of Lung Cancer 2021 World Conference on Lung Cancer revealed that almost two thirds of thoracic oncologists used telehealth for the first time during the COVID-19 pandemic. Oncologists reported that the top advantages of telehealth were continuity of care and maintenance of contact with patients; the most common barriers were a lack of resources for patients and regulatory limitations.
  • Cancer drugs granted FDA accelerated approval have stayed on the market after post-approval trials show no benefit (BMJ 2021;374:n1959). Researchers identified 10 cancer drugs granted accelerated approval for 18 indications in which post-approval trials failed to meet their primary endpoint. Drugs for 12 indications were withdrawn a median of 1.6 years after negative trial results were announced—with six withdrawals occurring in 2021. Drugs for six of the indications have remained on the market for a median of 1.7 years after negative results were released, and the National Comprehensive Cancer Network (NCCN) still recommends the drugs for eight indications.
  • The benefit of chemotherapy after surgery for metastatic colorectal cancer confined to the liver remains unclear (J Clin Oncol 2021 Sep 14 [Epub ahead of print]). In a phase II/III trial, patients treated with adjuvant chemotherapy had a 5-year disease-free survival rate of 49.8%, compared with 38.7% in those who didn’t receive chemotherapy. However, the 5-year overall survival rate was 71.2% in the chemotherapy arm versus 83.1% in the placebo arm.
  • The NCCN updated its guidelines for prostate cancer treatment. The guidelines now include the radioactive diagnostics gallium 68 PSMA-11 and piflufolastat F-18 (Pylarify; Progenics Pharmaceuticals) for prostate specific membrane antigen PET imaging. The FDA approved the agents in December 2020 and May 2021, respectively.
  • President Joseph Biden appointed seven new members to the National Cancer Advisory Board, which plays a role in guiding the director of the NCI, Ned Sharpless, MD. The appointees include John Carpten, PhD, of the University of Southern California's Keck School of Medicine in Los Angeles; Nilofer Azad, MD, of the Johns Hopkins Sidney Kimmel Cancer Center in Baltimore, MD; Luis Diaz Jr., MD, of Memorial Sloan Kettering Cancer Center in New York, NY; Christopher Friese, PhD, of the University of Michigan Rogel Cancer Center in Ann Arbor; Amy Heimberger, MD, of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago, IL; Ashani Weeraratna, PhD, also of Sidney Kimmel; and Karen Winkfield, MD, PhD, of the Vanderbilt-Ingram Cancer Center in Nashville, TN.

September 3–9

  • Adding lurbinectedin (Zepzelca; PharmaMar/Jazz Pharmaceuticals) to chemotherapy may not improve survival for patients with small cell lung cancer, according to findings presented at the International Association for the Study of Lung Cancer 2021 World Conference on Lung Cancer (WCLC). In the phase III ATLANTIS trial, the combination did not significantly improve median overall survival (OS) or progression-free survival (PFS) compared with chemotherapy alone. Lurbinectedin works by inhibiting transactivated transcription and modulating the tumor microenvironment.
  • Also at the WCLC, researchers reported that 14% of lung cancer deaths worldwide may be attributed to air pollution. The analysis combined data on lung cancer mortality with information on indoor and outdoor air pollution by country. People ages 50 to 69 in Serbia, Montenegro, North Macedonia, Bosnia and Herzegovina, and Poland had the highest risk of dying from lung cancer caused by pollution; for those over 70, the risk was highest in China, Mongolia, North Korea, Laos, and Montenegro.
  • Sanofi will buy Kadmon Holdings for $1.9 billion. Sanofi will gain belumosudil (Rezurock), a ROCK2 inhibitor approved earlier this year for certain patients with chronic graft-versus-host disease. Kadmon’s pipeline also includes therapies for immune and fibrotic diseases, as well as cancer immunotherapies.
  • Macrogenics announced that the monoclonal antibody margetuximab-cmkb (Margenza) plus chemotherapy may not benefit patients with metastatic, HER2-positive breast cancer. In a final analysis of the phase III SOPHIA trial, the investigational combination did not extend OS compared with trastuzumab plus chemotherapy. The FDA approved the agent last year based on improved PFS.
  • Multiple studies concluded that rovalpituzumab tesirine (Rova-T; Stemcentrx) may not be effective in small cell lung cancer. In the phase III TAHOE trial, patients treated with the agent had a shorter OS than those who received standard chemotherapy (J Thorac Oncol 2021;16:1547–58). In a phase I/II trial, combining Rova-T with immune checkpoint inhibitors led to significant side effects (J Thorac Oncol 2021;16:1559–69). And in a phase I trial, there was no benefit to adding Rova-T to chemotherapy (J Thorac Oncol 2021;16:1582–8). An antibody–drug conjugate, Rova-T binds to the ligand of the atypical Notch ligand delta-like protein 3 and delivers a cytotoxic payload of pyrrolobenzodiazepine.
  • Lung cancer in nonsmokers may arise from the accumulation of mutations caused by natural processes (Nat Genet 2021;53:1348–59). Researchers performed whole-genome sequencing on tissue from 232 patients with non–small cell lung cancer (NSCLC) who had never smoked. They found that none of the patients had mutational signatures associated with exposure to tobacco smoking—not even those exposed to secondhand smoke. However, the analysis revealed novel subtypes of NSCLC linked to the activation of progenitor cells, EGFR alterations, and whole-genome doubling.
  • Late mortality in people who had allogenic blood or bone marrow transplants has declined in the past four decades, although life expectancy is still shorter (JAMA Oncol 2021 Sep 9 [Epub ahead of print]). Researchers followed 4,741 people who had transplants between 1974 and 2014. They found that all-cause mortality and years of life lost decreased over time—and that the reduction in mortality was limited to those who had a transplant before age 18 and those who received bone marrow. Overall, the cohort experienced a 20.8% reduction in life expectancy compared with the general population.
  • Roche made a $150 million deal with Adaptimmune Therapeutics that could be worth more than $3 billion in milestone payments. The companies will collaborate on allogeneic cell therapies for five cancer targets, plus therapies for personalized treatment. Adaptimmune will handle early clinical development, and Roche will be responsible for later clinical testing and commercialization.

August 2021

August 27–September 2

  • The U.S. Court of Appeals for the Federal Circuit reversed a $1.2 billion ruling against Gilead for patent infringement. In the case, Bristol Myers Squibb (BMS) claimed that the chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (Yescarta) developed by Gilead subsidiary Kite Pharma infringed on a CAR T-cell patent held by BMS subsidiary Juno Therapeutics. BMS said it would seek a review of the decision.
  • The FDA approved zanubrutinib (Brukinsa; BeiGene) for patients with Waldenström macroglobulinemia. The approval was based on a noncomparative analysis of the phase III ASPEN trial, in which patients treated with the drug had a response rate of 77.5%, and a 12-month event-free duration of response rate of 94.4%. A Bruton tyrosine kinase inhibitor, zanubrutinib was previously approved for mantle cell lymphoma.
  • The FDA upgraded pembrolizumab’s (Keytruda; Merck) accelerated approval to a full approval for patients newly diagnosed with advanced or metastatic urothelial carcinoma but limited the indication to those who aren’t eligible for platinum-containing chemotherapy. The decision was based on the phase III KEYNOTE-361 trial, in which the PD-1 inhibitor did not extend overall survival or progression-free survival (PFS) in patients who received platinum-based chemotherapy.
  • Sesen Bio withdrew its European marketing application for the antibody–drug conjugate oportuzumab monatox-qqrs (Vicineum) in bladder cancer that doesn’t respond to bacillus Calmette-Guérin immunotherapy. In August, the FDA declined to approve the drug for the same indication, citing manufacturing issues and requesting additional clinical data and statistical analyses.
  • Roche announced it will withdraw U.S. marketing of the PD-L1 inhibitor atezolizumab (Tecentriq) plus chemotherapy in patients with inoperable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1. The agent was previously granted accelerated approval for this indication based on results of the phase III IMpassion130 trial. However, in the follow-up phase III IMpassion131 trials, the drug failed to extend PFS compared with chemotherapy alone.
  • Roche announced it will withdraw U.S. marketing of the PD-L1 inhibitor atezolizumab (Tecentriq) plus chemotherapy in patients with inoperable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1. The agent was previously granted accelerated approval for this indication based on results of the phase III IMpassion130 trial. However, in the follow-up phase III IMpassion131 trials, the drug failed to extend PFS compared with chemotherapy alone.
  • The National Comprehensive Cancer Network updated its COVID-19 vaccination guidelines for people with cancer (https://www.nccn.org/covid-19). The guidelines now recommend a third dose of an mRNA COVID-19 vaccine for groups that could be immunosuppressed, including patients with solid tumors treated within a year of their initial vaccine dose, patients with active blood cancer regardless of whether they are currently receiving treatment, and people who had a stem cell transplant or cell therapy, especially within 2 years.
  • New diagnoses of common cancers have significantly declined during the COVID-19 pandemic (JAMA Netw Open 2021;4:e2125681). Researchers analyzed 799,496 patient records, comparing those diagnosed with cancer before the pandemic (January 2019 to February 2020) to those diagnosed during three periods of the pandemic: March to May 2020, June to October 2020, and November 2020 to March 2021. Combined diagnoses for eight common cancers decreased by 29.8% during the first phase of the pandemic, by 9.6% in the second period, and by 19.1% in the most recent period.

August 20–26

  • Pfizer announced that it will acquire Trillium Therapeutics for $2.26 billion. Trillium’s lead drug candidates are the SIRPα–CD47 pathway blockers TTI-622 and TTI-621, which are being developed for hematologic malignancies. In early clinical trials, the drugs have shown activity in relapsed/refractory lymphoid malignancies and multiple myeloma.
  • Bristol Myers Squibb’s nivolumab (Opdivo) was approved as an adjuvant therapy for urothelial carcinoma in patients at high risk of recurrence after surgery. The approval was based on the phase III CHECKMATE-274 trial, in which patients treated with the PD-1 inhibitor had a median disease-free survival (DFS) of 20.8 months, compared with 10.8 months in those who received a placebo.
  • The FDA also approved the IDH1 inhibitor ivosidenib (Tibsovo; Servier) for patients with locally advanced or metastatic IDH1-mutant cholangiocarcinoma who have received prior treatment. The decision was based on the phase III Study AG120-C-005 trial, in which ivosidenib led to a median progression-free survival of 2.7 months, compared with 1.4 months for a placebo. Ivosidenib was previously approved for IDH1-mutant acute myeloid leukemia.
  • The FDA reminded patients and healthcare providers that information is lacking on the safety and effectiveness of robotically assisted surgical devices for mastectomy and other procedures to prevent or treat breast cancer. Such tools have been OK’d for other surgical procedures in patients with cancer, including hysterectomy, prostatectomy, and colectomy—although the FDA has not evaluated them based on cancer-related outcomes, such as overall survival, DFS, or disease recurrence.
  • The FDA denied marketing applications for more than 55,000 flavored electronic-cigarette (e-cigarette) products submitted by three companies. The agency claimed that there isn’t enough evidence that the items help adult smokers of combustible cigarettes to quit to outweigh the risk of widespread use among children. In total, more than 500 companies submitted applications for more than 6.5 million new tobacco products ahead of the September 9, 2020, deadline.
  • Novartis reported that tisagenlecleucel (Kymriah) may not be effective in patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma. In the phase III BELINDA trial, the therapy failed to extend event-free survival compared with chemotherapy. The chimeric antigen receptor T-cell therapy is FDA-approved for certain patients with acute lymphoblastic leukemia and large B-cell lymphoma.
  • Merck KGaA halted its phase II INTR@PID BTC 055 trial testing bintrafusp alfa plus gemcitabine and cisplatin in patients newly diagnosed with locally advanced or metastatic biliary tract cancer. The company made the decision after an independent data monitoring committee determined that the trial was unlikely to meet its overall survival endpoint. A bifunctional fusion protein that blocks TGFβ and PD-L1, bintrafusp alfa previously demonstrated a lack of effectiveness in another phase II trial in biliary tract cancer, as well as in a phase III trial in non–small cell lung cancer.
  • Stand Up To Cancer (SU2C) raised more than $183.3 million in pledges to support cancer research during its seventh biennial televised fundraising special. The event aired on more than 65 media platforms in the United States and Canada. The American Association for Cancer Research is SU2C’s scientific partner.

August 13–19

  • The FDA approved belzutifan (Welireg; Merck) for patients with renal cell carcinoma, central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors associated with von Hippel-Lindau disease who don’t require immediate surgery. The approval was based on the Study 004 trial, in which 61 patients had an overall response rate (ORR) of 49%, and 56% of responses lasted for at least 12 months. Belzutifan is the first hypoxia-inducible factor-2α inhibitor approved by the FDA.
  • The agency also granted accelerated approval to the PD-1 inhibitor dostarlimab-gxly (Jemperli; GlaxoSmithKline) in patients with mismatch repair (MMR)–deficient recurrent or advanced solid tumors. The approval was based on the phase I GARNET trial, in which patients had an ORR of 41.6%, and the median duration of response was 34.7 months. The agency also approved Roche’s VENTANA MMR RxDx Panel as a companion diagnostic.
  • The FDA declined to approve oportuzumab monatox-qqrs (Vicineum; Sesen Bio) for non–muscle invasive bladder cancer that doesn’t respond to bacillus Calmette-Guérin immunotherapy. In a letter to the company, the agency cited manufacturing issues and requested additional clinical data and statistical analyses. An investigation by STAT revealed more than 2,000 protocol violations during the clinical trial, plus instances of investigator misconduct and a failure to report a drug-related patient death. An antibody–drug conjugate, oportuzumab monatox-qqrs consists of a recombinant fusion protein targeting epithelial cell adhesion molecule attached to a payload of Pseudomonas exotoxin A.
  • Illumina closed its $8 billion purchase of Grail. The announcement came even as the Federal Trade Commission is suing to block the deal; the European Union is investigating the acquisition. Grail’s shareholders will be paid, but Grail will continue to run as a separate company so that the companies can be separated if regulators succeed at preventing the deal.
  • Researchers reported that Merck’s pembrolizumab (Keytruda) may be an effective adjuvant therapy for patients with clear-cell renal-cell carcinoma and a high risk of recurrence after nephrectomy (N Engl J Med 2021;385:683–94). In the phase III KEYNOTE-564 trial, patients treated with the PD-1 inhibitor had a 24-month disease-free survival rate of 77.3%, compared with 68.1% in patients who received a placebo.
  • The Society for Immunotherapy of Cancer published guidelines for treating breast cancer with immunotherapy (J Immunother Cancer 2021;9:e002597). The recommendations cover key aspects of treatment with immunotherapies, including diagnostic testing, treatment planning, side effects, and quality-of-life considerations. The guidelines were compiled by a panel of experts based on the published literature and their own clinical experience.
  • The Cancer Prevention & Research Institute of Texas in Austin awarded $142 million to researchers at 24 institutions and companies across the state. Several grants will be used to build a clinical trial network and increase participation and representation in clinical trials. In addition, some of the money will support research on improving chimeric antigen receptor T-cell therapy and overcoming resistance to immune checkpoint blockade.

August 6–12

  • The FDA authorized a third dose of the Pfizer/BioNTech and Moderna COVID-19 vaccines for people with a compromised immune system due to their increased risk of developing severe COVID-19 infections. The FDA defines this group as people who have received a solid organ transplant "or those who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise."
  • The agency also approved lenvatinib (Lenvima; Eisai) plus pembrolizumab (Keytruda; Merck) as a first-line treatment for patients with advanced renal cell carcinoma. The approval is based on the phase III CLEAR trial (Study 307/KEYNOTE-581) in which patients treated with the combination had a median progression-free survival of 23.9 months and an objective response rate of 71%, compared with 9.2 months and 36%, respectively, in patients who received sunitinib (Sutent; Pfizer), the current standard of care.
  • A California appeals court upheld an $86 million verdict against Bayer. The lawsuit was brought by customers who claimed that high use of Bayer's glyphosate-based weedkillers such as Roundup caused them to develop cancer. The company, which has appealed the verdict three times, will now file a petition with the U.S. Supreme Court.
  • The quality of real-world data (RWD) for novel cancer drugs may be lacking (Eur J Cancer 2021;6:136–44). Researchers analyzed 293 RWD studies for 45 drugs to treat solid tumors approved by the FDA and the European Medicines Agency between 2010 and 2015. They found that 78% of RWD studies were classified as low quality, and the differences in median survival between the RWD studies and the corresponding clinical trials range from -32 months to 21 months. Lower-quality studies were more likely to report better survival outcomes than higher-quality studies.
  • The FDA finalized guidance on using metastasis-free survival (MFS) as an endpoint in clinical trials for nonmetastatic castration-resistant prostate cancer (https://www.fda.gov/media/117792/download). The document outlines considerations for using MFS as an endpoint, including defining MFS prior to the start of a trial and stratifying patients based on previous therapy and PSA doubling time. It also makes recommendations for the type and frequency of imaging, as well as how to interpret trial results.
  • The agency also placed two partial clinical holds on trials evaluating eprenetapopt (Aprea Therapeutics) in myeloid malignancies and lymphoid cancers. Aprea did not disclose the reason for the first hold; the second hold came after FDA raised concerns about safety and efficacy data in the phase III MDS trial. Eprenetapopt is a small molecule that reactivates mutant TP53.
  • MyLAB Box announced the launch of its at-home colorectal cancer screening test. The fecal immunochemical test works by screening for blood in the stool, which can indicate the presence of colon cancer or other digestive tract conditions. The FDA approved the similar Cologuard screening test in 2014.

July 30–August 5

  • Bayer will acquire Vividion Therapeutics for $1.5 billion up front and up to $500 million more in milestone payments. Bayer will gain Vividion's small-molecule discovery platform, which will be used to develop oncology and immunology targets. Vividion’s lead program includes a transcription factor NRF2 antagonist being investigated for the treatment of NRF2-mutant cancers.
  • Bristol Myers Squibb announced it will stop U.S. marketing of romidepsin (Istodax) for patients with peripheral T-cell lymphoma who have previously received at least one therapy. The decision comes after the agent plus chemotherapy fail to extend progression-free survival (PFS) compared with chemotherapy alone in a phase III trial. A histone deacetylase inhibitor, romidepsin was granted accelerated approval by the FDA in 2011.
  • Based on the recommendation of an independent data monitoring committee, Regeneron Pharmaceuticals halted a phase III trial of cemiplimab-rwlc (Libtayo) plus chemotherapy early due to strong results. In the EMPOWER-Lung 3 trial, patients newly diagnosed with advanced non–small cell lung cancer (NSCLC) treated with the PD-1 inhibitor–chemotherapy combination had a median overall survival (OS) of 22 months, compared with 13 months in those who received chemotherapy alone.
  • The European Commission approved the PD-1 inhibitor nivolumab (Opdivo; Bristol Myers Squibb) as an adjuvant therapy for patients with esophageal or gastroesophageal junction cancer who have residual pathologic disease after neoadjuvant chemoradiotherapy. The decision was based on the phase III CheckMate-577 trial, in which adjuvant nivolumab extended disease-free survival by 5.6 months compared with a placebo.
  • The investigational agent plinabulin (BeyondSpring) plus docetaxel may be effective in patients with NSCLC who have received other therapies. In the phase III DUBLIN-3 trial, patients treated with the combination had a 24-month OS rate of 22.1% and a 48-month OS rate of 10.6%, compared with 12.5% and 0%, respectively, in patients who received docetaxel alone. Plinabulin is a selective immunomodulating microtubule-binding agent that induces antigen-presenting cells.
  • Researchers reported that avapritinib (Ayvakit; Blueprint Medicines) may not provide a benefit over regorafenib (Stivarga; Bayer) in patients with locally advanced inoperable or metastatic gastrointestinal stromal tumors (GIST; J Clin Oncol 2021 Aug 3 [Epub ahead of print]). In the phase III VOYAGER trial, the agent did not improve median PFS compared with regorafenib; median OS data are still immature. Avapritinib inhibits mutant KIT and platelet-derived growth factor receptor-alpha (PDGFRA) kinases; it is FDA approved for patients with inoperable or metastatic GIST who have PDGFRA exon 18 mutations.

July 2021

July 23–29

  • A judge in California ordered Novartis to pay $177.8 million to Plexxikon, a subsidiary of Daiichi Sankyo. The judge ruled that Novartis’s BRAF inhibitor dabrafenib (Tafinlar), which it acquired from GlaxoSmithKline and developed in collaboration with Roche, infringed on two patents Plexxikon holds for its BRAF inhibitor, vemurafenib (Zelboraf.) Both agents are FDA approved to treat melanoma; Plexxikon claimed that Novartis could only develop dabrafenib based on information it gained about vemurafenib during partnership talks.
  • The U.S. House of Representatives passed an appropriations package for fiscal year (FY) 2022. The package contains a bill proposing an increase of $6.5 billion for the NIH, which would bring its total budget to $49 billion. The additional funds include a $3.5 billion increase in base funding, as well as $3 billion to establish the Advanced Research Projects Agency for Health. The U.S. Senate has yet to take up appropriations bills for FY22.
  • Amgen will acquire Teneobio for $900 million upfront and up to $1.6 billion more in milestone payments. Amgen will gain Teneobio’s bispecific T-cell engager, TNB-585, which is in phase I testing against metastatic castrate-resistant prostate cancer, as well as the company’s bispecific and multispecific antibody technologies.
  • The FDA approved the PD-1 inhibitor pembrolizumab (Keytruda; Merck) for yet another indication: It can now be combined with chemotherapy for neoadjuvant use in patients with high-risk, early-stage, triple-negative breast cancer, followed by pembrolizumab monotherapy after surgery. The approval was based on the phase III KEYNOTE-522 trial, in which patients treated with the combination had a pathological complete response rate of 63%, compared with 56% for those who received chemotherapy alone.
  • Bristol-Myers Squibb will stop U.S. marketing of its PD-1 inhibitor, nivolumab (Opdivo), for patients with hepatocellular carcinoma who were previously treated with sorafenib (Nexavar; Bayer/Onyx.) The decision follows an FDA advisory committee’s recommendation to remove the drug from the market for this indication due to a lack of evidence supporting its accelerated approval.
  • Incyte announced that the FDA declined to approve its PD-1 inhibitor, retifanlimab (INCMGA0012), for patients with locally advanced or metastatic anal cancer who have already received platinum-based chemotherapy. In a response letter to the company, the FDA stated that additional data are needed to demonstrate the clinical benefit of the drug. The response follows an FDA advisory committee’s June recommendation to defer a final decision until results of the phase III POD1UM-303 trial are available.
  • The FDA issued an alert that patients with multiple myeloma may have an increased risk of death if they are treated with melphalan flufenamide (Pepaxto; Oncopeptides AB) plus dexamethasone. The warning came after researchers announced that patients treated with the combination in the phase III OCEAN, Study OP-103 trial had a median overall survival of 19.7 months, compared with 25 months in those who received pomalidomide (Pomalyst; Celgene). The FDA granted accelerated approval for the combination in relapsed/refractory multiple myeloma in February.
  • The American Society for Radiation Oncology (ASTRO) issued recommendations for treating soft tissue sarcoma with radiation (Pract Radiat Oncol 2021 Jul 25 [Epub ahead of print]). Among other things, ASTRO strongly recommends radiation therapy before surgery over radiation after surgery for patients who require such therapy. The guidance—the first for soft tissue sarcoma—is based on a systematic review of the literature.

July 16–22

  • Pfizer announced that it will pay Arvinas $1 billion up front in a deal that could be worth up to $1.4 billion more in milestone payments. The deal centers on Arvinas’s proteolysis-targeting chimera ARV-471, an estrogen receptor protein degrader that is being tested in phase I and II trials of ER-positive, HER2-negative breast cancer. Moving forward, the companies will split development and commercialization costs of the drug, as well as profits.
  • The FDA approved the ROCK2 inhibitor belumosudil (Rezurock; Kadmon Pharmaceuticals) for patients with chronic graft-versus-host disease following hematopoietic stem cell transplantation who have already received two systemic therapies. The approval was based on the phase II ROCKstar (KD025-213) trial, in which 75% of patients responded to the drug, with a median duration of response of 1.9 months.
  • The agency also granted full approval to pembrolizumab (Keytruda; Merck) plus lenvatinib (Lenvima; Eisai) to treat patients with certain advanced endometrial carcinomas based on positive progression-free survival and overall survival (OS) results in the phase III KEYNOTE-775/Study 309 trial. The FDA granted the combination an accelerated approval in September 2019.
  • Social media may spread misinformation and harmful information about cancer (J Natl Cancer Inst 2021 Jul 22 [Epub ahead of print]). Researchers analyzed 200 of the most popular social media articles on the four most common cancers: breast, prostate, lung, and colorectal. Overall, 32.5% of the stories included inaccurate information, and 30.5% contained harmful information. Moreover, the median number of engagements on social media was higher for the misleading and injurious articles than for the factual pieces.
  • China's National Medical Products Administration OK’d the PD-L1 inhibitor durvalumab (Imfinzi; AstraZeneca) plus chemotherapy for extensive-stage small-cell lung cancer. The approval is based on the phase III CASPIAN trial, in which patients treated with the combination had a median overall OS of 12.9 months, compared with 10.5 months in those who received only chemotherapy. The FDA approved the drug for this indication in March 2020.
  • Bristol Myers Squibb announced that the PD-1 inhibitor nivolumab (Opdivo) plus the CTLA4 inhibitor ipilimumab (Yervoy) did not extend OS compared with chemotherapy in patients newly diagnosed with recurrent or metastatic squamous cell carcinoma of the head and neck. The company also reported that the immunotherapy combination failed to improve OS in a subgroup of patients with high PD-L1 expression in the phase III CheckMate-651 trial.
  • The NCI renewed the comprehensive cancer center designation for the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center in Baltimore. The agency also awarded the center almost $13 million in funding over 5 years. Since 2016, the number of patients enrolled in trials at Greenebaum has increased by 167%; almost 56% of trial participants are minorities.

July 9–15

  • The FDA upgraded enfortumab vedotin-ejfv’s (Padcev; Astellas/Seattle Genetics) accelerated approval to a full approval for patients with locally advanced or metastatic urothelial cancer who have already received a PD-1–PD-L1 therapy and a platinum-containing chemotherapy. The agency also expanded the indication to include patients with locally advanced or metastatic disease who have received at least one prior therapy and aren’t eligible for chemotherapy. The decision was based on positive results in the EV-301 and EV-201 trials. Enfortumab vedotin-ejfv is a Nectin-4–directed antibody–drug conjugate.
  • The agency also approved daratumumab and hyaluronidase-fihj (Darzalex Faspro; Janssen) plus pomalidomide and dexamethasone for patients with multiple myeloma who have already received at least one therapy. The approval is based on the phase III APOLLO trial, in which patients treated with the investigational combination had a median progression-free survival of 12.4 months, compared with 6.9 months for those who received only pomalidomide and dexamethasone. Daratumumab and hyaluronidase-fihj is a subcutaneous form of the intravenous monoclonal antibody daratumumab.
  • The U.S. House of Representatives Subcommittee on Labor, Health and Human Services, and Education marked up its appropriations bill for the 2022 fiscal year. The bill proposes $49 billion in funding for the NIH, an increase of $6.5 billion. This includes an increase of $3.5 billion in NIH base funding, as well as $3 billion to establish the Advanced Research Projects Agency for Health. The funding would boost the NCI budget by $432 million to $7 billion, which would include $194 million for the Cancer Moonshot.
  • Communication of overall survival (OS) data varies considerably on cancer drug labels (JAMA Intern Med 2021 Jul 12 [Epub ahead of print]). Researchers analyzed labels for 50 drug indications approved between 2014 and 2018—23 of which reported OS based on interim analyses and 27 of which reported final OS. Twenty of the 23 labels stated that the drug did not have a significant OS benefit in interim analyses or that OS data were not yet mature; 12 of the 27 labels did not report the statistical significance of OS findings.
  • MRI may be a useful tool for guiding prostate biopsies in men with high PSA levels (N Engl J Med 2021 Jul 9 [Epub ahead of print]). In a trial of 1,532 men with a PSA of at least 3 ng/mL, 929 had an MRI followed by a biopsy if indicated, and 603 had a biopsy without imaging. In total, 21% of men in the MRI group were diagnosed with clinically significant cancer and 4% were diagnosed with clinically insignificant cancer, compared with 18% and 12%, respectively, in the nonimaging biopsy group.
  • Globally, 4.1% of new cancer cases in 2020 could be attributed to alcohol consumption (Lancet Oncol 2021 Jul 13 [Epub ahead of print]). Researchers combined estimates of alcohol intake per person per country in 2010 with data on new cancer cases in 2020. They found that 568,700 men and 172,600 women were diagnosed with alcohol-associated cancers—most commonly esophagus, liver, or breast cancer. Risky and heavy drinking were linked to the largest proportion of alcohol-related cancer cases: 39% and 47%, respectively.
  • The FDA lifted a partial clinical hold on a phase Ib trial testing the CDK8/CDK19 inhibitor RVU120 (SEL120; Ryvu Therapeutics) in relapsed/refractory acute myeloid leukemia and high-risk myelodysplastic syndrome. The hold was placed while the agency investigated a patient death. The company will modify its protocol to increase safety, taking steps such as tightening exclusion criteria and increasing patient monitoring.
  • Johnson & Johnson recalled five aerosol sunscreens after finding that they contained trace amounts of benzene. The carcinogen, which is not an ingredient used in sunscreen, was present in four Neutrogena sunscreens, as well as one Aveeno product. Long-term exposure to benzene can cause leukemia and other cancers.

July 2–8

  • The World Health Organization (WHO) released new guidelines for cervical cancer screening (available at https://www.who.int). The agency recommends human papillomavirus (HPV) DNA testing rather than Pap testing or visual inspection with acetic acid, citing the test’s greater accuracy and simplicity, as well as its ability to detect the high-risk strains of HPV that cause most cervical cancers. The WHO also recommends greater access to self-sampling for testing, as well as earlier—starting at age 25 instead of 30—and more frequent screening for women with HIV, who are more likely to develop cervical cancer.
  • The FDA finalized guidance on evaluating cancer drugs in patients with brain metastases (https://www.fda.gov/media/141507/download). The document provides recommendations for designing trials to test cancer agents in these patients—including how to decide which patients to include, how to factor in previous treatments, how to assess brain metastases, and how to select study endpoints. It also notes when drug labels should describe the effects of treatment on central nervous system metastases.
  • Merck announced that the FDA expanded the approval for pembrolizumab (Keytruda) to include patients with locally advanced cutaneous squamous cell carcinoma that cannot be treated with surgery or radiation. The expanded approval is based on the phase II KEYNOTE-629 trial, in which 50% of patients responded to the drug, and 81% of responses lasted for at least 6 months. The drug is already approved for patients with recurrent or metastatic disease who lack other treatment options.
  • Researchers reported that racial disparities in breast cancer screening have worsened during the COVID-19 pandemic (Cancer Cell 2021 July 1 [Epub ahead of print]). After a substantial decrease in breast cancer screening between March and June 2020, it rebounded to prepandemic levels between September and December 2020. However, this was not the case for Black and Hispanic women, who were less likely to have mammograms during this period than they were before the pandemic.
  • Bayer and Onyx Pharmaceuticals jointly filed suit against Dr. Reddy’s Laboratories over its proposed generic version of Nexavar (sorafenib), an FDA-approved multikinase inhibitor for certain thyroid, liver, and kidney cancers. According to the complaint, Dr. Reddy’s submitted an Abbreviated New Drug Application for approval of the generic version in May, thus suggesting that the Bayer–Onyx Nexavar patent is invalid or would not be infringed upon by the generic.
  • Regulators in 14 European countries have failed to ensure publication of a significant amount of trial data. Results are missing from at least 5,976 single-country clinical trials, mostly from studies in Italy (1,221), Spain (884), and the Netherlands (839). Additionally, results reporting was especially poor in the Netherlands—just 10% of trials—followed by Italy and France, both at 17%. The report, published by Transparency International France, Health Action International, Melanoma Patient Network Europe, and TranspariMED, is available at http://freepdfhosting.com/3b527e1675.pdf.

June 2021

June 25–July 1

  • JUUL agreed to pay North Carolina $40 million to settle a lawsuit involving the company’s electronic cigarettes (e-cigarettes). The state argued that JUUL’s marketing practices for e-cigarettes led to widespread nicotine addiction among young people. Thirteen other states have filed similar lawsuits against JUUL, along with almost 2,000 cases filed by cities, counties, school districts, and other entities.
  • Iovance Biotherapeutics' LN-145 may have activity against relapsed/refractory metastatic non–small cell lung cancer (NSCLC). In the IOV-COM-202 basket trial, six of 28 patients with NSCLC responded to the therapy, and 12 more experienced stable disease. A tumor-infiltrating lymphocyte therapy, LN-145 has previously elicited responses in melanoma and cervical cancer.
  • BeiGene's PD-1 inhibitor tislelizumab may benefit patients with inoperable hepatocellular carcinoma who have received prior therapies, according to research reported at the European Society for Medical Oncology World Congress on Gastrointestinal Cancer 2021. In a phase II trial, 12.4% of patients responded to the drug; median overall survival (OS) was 12.4 months and median progression-free survival was 2.7 months.
  • The FDA approved asparaginase erwinia chrysanthemi (recombinant)-rywn (Rylaze; Jazz Pharmaceuticals) as a component of multiagent chemotherapy for patients with acute lymphoblastic leukemia or lymphoblastic lymphoma who are allergic to asparaginase derived from E. coli. The approval was based on the phase II/III Study JZP458-201 trial, in which 94% of patients achieved the target level of asparaginase activity after being treated with the recommended dose. The approval is expected to help resolve an ongoing shortage of the only other FDA-approved option for such patients.
  • The CD19-directed chimeric antigen receptor therapy axicabtagene ciloleucel (Yescarta; Kite) may lead to better responses than standard therapy in patients with relapsed/refractory large B-cell lymphoma. In the ZUMA-7 trial, the therapy significantly extended event-free survival and increased the response rate compared with chemotherapy and a stem cell transplant—and patients trended toward longer OS.
  • Researchers reported that screening for breast and cervical cancers dropped dramatically after the COVID-19 pandemic began (Preventive Medicine 2021;151:106559). In April 2020, breast cancer screening declined by 87% and cervical cancer screening decreased by 84%, compared with the previous 5-year averages for the month. However, screening rates had started to recover by June 2020, when the study period ended.
  • Two organizations called for the inclusion of patients with cancer in COVID-19 vaccine trials in a joint statement available at https://www.asco.org/. The American Society of Clinical Oncology and Friends of Cancer Research pointed out that patients with cancer may be more vulnerable to COVID-19 than healthy people, but they have almost universally been excluded from vaccine trials, making it difficult to assess whether vaccines are safe and effective for them.

June 18–24

  • NIH director Francis Collins, MD, PhD, and Eric Lander, PhD, director of the Office of Science and Technology Policy, and others described the thinking behind the Advanced Research Projects Agency for Health (ARPA-H) within the NIH (Science 2021 Jun 22 [Epub ahead of print]). President Joe Biden proposed creating ARPA-H "to develop breakthroughs—to prevent, detect, and treat diseases like Alzheimer’s, diabetes, and cancer," and requested $6.5 billion to fund it in the 2022 fiscal year budget. Inspired by the Defense Advanced Research Projects Agency, ARPA-H would stress flexibility, nimbleness, speed, and efficiency in advancing biomedical research.
  • The FDA Oncologic Drugs Advisory Committee voted 13 to 4 to defer a recommendation on retifanlimab (MGA012; MacroGenics) for anal cancer until more data are available. In the phase II POD1UM-202 trial, 14% of patients with locally advanced or metastatic anal cancer previously treated with platinum-based chemotherapy responded to the PD-1 inhibitor. The committee is awaiting results from the phase III POD1UM-303 trial.
  • Researchers identified mutations in children with rhabdomyosarcoma that may be linked to poorer survival (J Clin Oncol 2021 Jun 24 [Epub ahead of print]). They performed next-generation sequencing on samples from 641 patients with the disease enrolled in clinical trials between 1995 and 2017. They found that patients with TP53 or MYOD1 mutations had shorter event-free survival than those without the mutations, and TP53 alterations were associated with more aggressive disease.
  • Corcept Therapeutics announced it will halt a phase III trial testing the antiglucocorticoid relacorilant plus chemotherapy in patients with metastatic pancreatic cancer who had already received treatment. In the trial, two of 31 evaluable patients responded, suggesting that the combination is active but not sufficiently beneficial to warrant additional study. The company will continue to investigate the drug in other solid tumors.
  • The FDA released a draft guidance on expanding eligibility for oncology trials (https://www.fda.gov/media/150244/download). The document provides recommendations for designing trials that include patients with incurable cancer who have not yet received treatment, with the goal of increasing therapeutic options for these patients. The guidance is available for comment until August 24.
  • AbbVie announced it will exercise its right to acquire TeneoOne for an undisclosed sum. The deal centers on TeneoOne’s CD3/BCMA-targeting bispecific TNB-383B, which elicited an objective response rate of 79% in a phase I trial of relapsed/refractory multiple myeloma. AbbVie partnered with TeneoOne to develop TNB-383B in February 2019.

June 11–17

  • In a deal worth at least $650 million, including $200 million in expenses, Bristol Myers Squibb will collaborate with Eisai to develop and commercialize MORAb-202, an antibody–drug conjugate that combines Eisai’s antifolate receptor alpha (FRα) antibody and its anticancer agent eribulin using an enzyme-cleavable linker. Eisai is investigating the agent in FRα-positive solid tumors, including endometrial, ovarian, lung, and breast cancers, in early-phase trials in Japan and the United States. Eisai is entitled to receive up to $2.45 billion more in milestone payments.
  • iTeos Therapeutics and GlaxoSmithKline (GSK) announced an agreement to jointly develop and commercialize EOS-448, an anti-TIGIT monoclonal antibody being investigated in a phase I trial as a treatment for patients advanced solid tumors. TIGIT, part of the CD226 checkpoint axis, has demonstrated potential as a target for the next generation of immune-oncology therapies. Under the deal—which will give GSK access to antibodies that synergistically target TIGIT, CD96, and PVRIG, the three known CD226 checkpoints—iTeos will receive an up-front payment of $625 million with up to $1.45 billion more for meeting development and commercial milestones.
  • The FDA greenlighted avapritinib (Ayvakit; Blueprint Medicines) for adults with advanced systemic mastocytosis (AdvSM), including those with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematologic neoplasm, and mast cell leukemia. The approval was based on results of the EXPLORER and PATHFINDER trials, which enrolled patients with AdvSM. The overall response rate in both trials combined was 57%, split almost evenly between complete and partial responses. The median duration of response was 38.3 months, and the median time to response was 2.1 months.
  • Oncologists should offer 1 year of adjuvant olaparib to patients with high-risk early-stage HER2-negative breast cancer and germline BRCA1/2 mutations following the completion of (neo)adjuvant chemotherapy and local treatment, including radiation, according to recommendations updating a 2020 guideline from the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology. The recommendation is based on the OlympiA trial, which demonstrated a significant improvement in invasive and disease-free survival with the PARP inhibitor compared with placebo.
  • Some patients with ovarian cancer are more likely to beat the disease if they have surgery prior to receiving chemotherapy instead of the other way around, according to a just-published analysis (PNAS 2021;118:e2026663118). Due to ongoing debate about the sequencing of therapies, researchers built a mathematical model, combined with clinical data from patients, to determine the best approach. For patients who were well enough to undergo an operation, surgery proved superior because it offers the best chance to remove cells likely to be resistant to chemotherapy, the researchers said.

June 4–10
This week: Special content from the 2021 ASCO meeting and other news

  • At the American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, researchers presented results indicating that the second-generation BTK inhibitor acalabrutinib (Calquence; AstraZeneca) has similar efficacy as ibrutinib (Imbruvica; Janssen) but is better tolerated in patients with previously treated chronic lymphocytic leukemia. In the phase III ELEVATE-RR trial, patients in both groups had a median progression-free survival (PFS) of 38.4 months. However, those treated with acalabrutinib were less likely to experience cardiac side effects, as well as grade 3 or higher adverse events (AE)—and were less likely to discontinue treatment or die due to AEs.
  • A pair of clinical trials suggest that Loxo Oncology’s TRK inhibitor larotrectinib (Vitrakvi) may be active in pediatric and adult patients with central nervous system (CNS) tumors and TRK fusions. In combined results from the NAVIGATE and SCOUT trials, the drug elicited responses in 10 of 33 patients, leading to a median PFS of 18.3 months; median overall survival (OS) was not reached. "These results support testing for NTRK gene fusions for all patients with CNS tumors, especially if there is no known driver," concluded Sébastien Perreault, MD, of CHU Sainte Justine in Montreal, Canada, who presented the results at the ASCO meeting.
  • At the ASCO meeting, researchers reported that Immunogen’s mirvetuximab soravtansine (IMGN853) plus bevacizumab (Avastin; Genentech) may benefit patients with recurrent ovarian cancer and high folate receptor alpha (FRα) expression. In a phase I/II trial, the combination elicited responses in 21 of 33 patients with FRα-high disease, and responses lasted for a median of 11.8 months; patients had a median PFS of 10.6 months. Mirvetuximab soravtansine is an antibody–drug conjugate that targets FRα in tumor cells and delivers tubulin-targeting maytansinoid DM4.
  • The PD-1 inhibitor toripalimab (Junshi Biosciences) plus chemotherapy may be an effective first-line treatment in patients with locally advanced, recurrent, or metastatic nasopharyngeal carcinoma. In the phase II JUPITER-02 trial, patients treated with the combination had a median PFS of 11.7 months and a 1-year PFS of 49%, compared with 8 months and 28%, respectively, in those who received chemotherapy alone. Findings were presented at the ASCO meeting.
  • "Over the last 20 years, we hit a glass ceiling in the first-line systemic treatment of advanced esophageal cancers, and apart from those cancers that were amplified for HER2, there was relatively little progress," said David Cunningham, MD, of the Royal Marsden NHS Foundation Trust in the UK, during the ASCO meeting. However, based on the results of the ESCORT-1st and CheckMate 648 studies, he said that a combination of immunotherapy and chemotherapy or dual immunotherapies should be deemed standard-of-care first-line treatment for esophageal squamous cell carcinoma.
  • Adding 177Lu-PSMA-617 to standard-of-care therapy may improve survival in patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer who have received other therapies. In the phase III VISION trial, patients treated with the agent plus standard-of-care therapy had a median radiographic PFS of 8.7 months and a median OS of 15.3 months, compared with 3.4 months and 11.3 months, respectively, in those who received standard-of-care therapy alone. 177Lu-PSMA-617 is a radionuclide that targets PSMA-expressing cancer cells with beta radiation. Results were presented at the ASCO meeting.
  • A 70-gene signature may identify patients with inoperable invasive breast cancer who are unlikely to relapse. In the phase III MINDACT trial, 1,000 women classified by the MammaPrint signature as having an ultralow risk of recurrence had an 8-year distant metastasis-free interval of 97% and an 8-year breast cancer–specific survival of 99.6%. "These patients could be candidates for further de-escalation of treatments, thus further reducing overtreatment and the risk of side effects," concluded Josephine Lopes Cardozo, MD, of the Netherlands Cancer Institute in Amsterdam, who presented the results at the ASCO meeting.
  • Also at the ASCO meeting, researchers reported early signs of activity for CYT-0851 (Cyteir) in patients with relapsed/refractory hematologic malignancies and advanced solid cancers. In a phase I trial, three of 21 evaluable patients responded to the drug—including patients with diffuse large B-cell lymphoma, follicular lymphoma, and soft-tissue sarcoma—and 10 more patients experienced stable disease. CYT-0851 is a small-molecule inhibitor of RAD51-mediated homologous recombination.
  • Cardinal Health Nuclear & Precision Health Solutions announced that the radioactive diagnostic agent Lymphoseek has been approved by the FDA for use in children. In addition to adult use, the new indication will provide an efficient, accurate, and safe way to enhance lymphatic mapping and guide sentinel lymph node biopsies in children with melanoma, rhabdomyosarcoma, or other solid tumors.

May 28–June 3

  • The FDA granted accelerated approval to sotorasib (Lumakras; Amgen) for patients with KRASG12C-mutated non–small cell lung cancer who have already received at least one therapy. In the phase II CodeBreak 100 trial, which formed the basis of the approval, the drug elicited an objective response rate (ORR) of 36% and a median duration of response (DoR) of 10 months. Sotorasib is the first KRAS inhibitor to be approved by the FDA.
  • The agency also granted accelerated approval to infigratinib (Truseltiq; BridgeBio Pharma) for patients with locally advanced or metastatic cholangiocarcinoma who have an FGFR2 fusion or other rearrangement and previously received other therapies. The decision was based on a phase II trial in which 108 patients had an ORR of 23% and a median DoR of 5 months. The approval is the first for infigratinib, an FGFR tyrosine kinase inhibitor.
  • MorphoSys announced it will acquire Constellation Pharmaceuticals for $1.7 billion. Constellation’s lead candidate is the BET inhibitor pelabresib (CPI-0610), which is being tested in a phase III trial in patients with myelofibrosis. The company is also developing the second-generation EZH2 inhibitor CPI-0209, which is being investigated in a phase II trial in solid and hematologic malignancies.
  • Bristol Myers Squibb (BMS) is being sued for $6.4 billion over its CAR T-cell therapy lisocabtagene maraleucel (Breyanzi) that was approved for large B-cell lymphoma in February 2021. According to the complaint, the company failed to make the required "diligent efforts" to seek FDA approval of the drug by a deadline of December 31, 2020, and thus avoided paying the sum to Celgene shareholders. BMS bought Celgene for $80.3 billion in November 2019.
  • AstraZeneca’s PARP inhibitor olaparib (Lynparza) may be an effective adjuvant therapy for patients with high-risk HER2-negative early breast cancer and a BRCA1/2 mutation who have had surgery and received neoadjuvant or adjuvant chemotherapy (N Engl J Med 2021 Jun 3 [Epub ahead of print]). At a median follow-up of 2.5 years in the phase III OlympiA trial, patients treated with the drug had an estimated 3-year invasive disease-free survival (DFS) rate of 85.9% and a 3-year distant DFS of 87.5%, compared with 77.1% and 80.4%, respectively, in patients who received a placebo. Findings will be presented at the 2021 American Society of Clinical Oncology Annual Meeting on June 6.

May 2021

May 21–27

  • The FDA granted accelerated approval to amivantamab-vmjw (Rybrevant; Janssen) for patients with non–small cell lung cancer and EGFR exon 20 insertion mutations who have already received platinum-based chemotherapy. The approval was based on the phase I CHRYSALIS trial, in which 81 patients had an overall response rate of 40% and a median duration of response of 11.1 months. Amivantamab-vmjw is a bispecific antibody that targets EGFR and MET.
  • U.S. legislators introduced the Long-term Opportunities for Advancing New Studies (LOANS) for Biomedical Research Act, which would authorize $30 billion over 3 years to support research in areas of unmet medical need, as well as research affected by the COVID-19 pandemic. The money would back so-called “BioBonds” of up to $25 million that would be given to small companies and universities. The legislation needs to be approved by the Senate and House of Representatives before it becomes law.
  • The U.S. Supreme Court declined to review a federal appeals court decision to include two U.S. scientists on eight immunotherapy patents. The scientists—Gordon Freeman, PhD, of Dana-Farber Cancer Institute in Boston, MA, and Clive Wood, PhD, of Boehringer Ingelheim—will be added to the patents, which were previously issued to Ono Pharmaceutical and Tasuku Honjo, MD, PhD, of Kyoto University in Japan. The patents describe the PD-1 pathway that is central to the development of PD-1/PD-L1 inhibitors.
  • The FDA published a final guidance on the development of bispecific antibodies (https://www.fda.gov/media/123313/download). The document outlines considerations and recommendations for pharmacology and manufacturing, as well as preclinical and clinical testing of the therapies. It also discusses differences in developing bispecific and monoclonal antibodies. Currently, blinatumomab (Blincyto; Amgen) and amivantamab-vmjw are the only bispecific antibodies approved for cancer, although various others are in clinical trials.
  • The agency also released a guidance on implementation of the Research Acceleration for Cure and Equity for Children Act. The 2017 act requires trial sponsors to evaluate molecularly targeted cancer drugs for adults in children if the same target is present (https://www.fda.gov/media/133440/download). Among other things, the guidance offers information about waivers and deferrals, describes safeguards for children enrolled in trials, and specifies the sources used to develop lists of relevant molecular targets.
  • A study revealed that the reporting of results from oncology trials has increased over the past 10 years (JAMA Netw Open 2021;4:e2110438). Researchers analyzed 12,240 oncology trials registered on ClinicalTrials.gov between 2007 and 2017 that were completed or terminated before September 2017. They found that results were reported for 60.7% of trials, and the 24-month reporting rate increased by 34% during the study period; more recent and larger trials were more likely to have results reported, as were those funded by the NIH.

May 14–20

  • The U.S. Preventive Services Task Force recommended colorectal cancer screening for people ages 45 to 70 (JAMA 2021;325:1965–77). Previously, the agency recommended that screening start at age 50. The change was based on research demonstrating the benefits of earlier screening, as well as a rising number of cases of early-onset colorectal cancer, defined as cancer diagnosed before age 50.
  • Bristol Myers Squibb (BMS) announced that the FDA approved its PD-1 inhibitor nivolumab (Opdivo) for patients with esophageal or gastroesophageal junction cancer who have residual pathologic disease after surgery and neoadjuvant chemoradiotherapy. The approval was based on the phase III CheckMate-577 trial, in which nivolumab led to a median disease-free survival (DFS) of 22.4 months, compared with 11 months in the placebo arm.
  • At a press preview for the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, researchers reported that atezolizumab (Tecentriq; Roche) following surgery and chemotherapy may stave off recurrence of non–small cell lung cancer. In the phase III IMpower010 trial, patients treated with the PD-L1 inhibitor had a median DFS of 42.3 months, compared with 35.3 months in patients who received best supportive care. The ASCO meeting will be held virtually June 4–8.
  • BMS announced a $200 million deal with Agenus that could be worth up to $1.36 billion more in milestone payments. BMS will acquire rights to Agenus’s anti-TIGIT agent AGEN1777, which is in preclinical testing for various solid cancers. BMS is also developing its own anti-TIGIT drug, BMS-986207.
  • An American Cancer Society review of cancer prevention and early detection measures concluded that smoking reached a historic low of 14% in 2019 (Cancer Prevention & Early Detection Facts & Figures 2021-2022). However, cancer screening could be improved: In 2018, 63% of eligible women were up to date with breast screening and 84% with cervical cancer screening; 66% of eligible adults were up to date with colorectal cancer screening. Only 5% to 6% of eligible adults received lung cancer screening.
  • The Cancer Prevention & Research Institute of Texas in Austin awarded $69.5 million in grants to researchers at Texas institutions, including Baylor College of Medicine in Houston and The University of Texas at Austin. Some of the money will be used to expand existing cancer prevention programs for people who lack sufficient access to medical care, focusing on tobacco cessation, mammography, and colorectal cancer screening.

May 7–13

  • Clovis Oncology's rucaparib (Rubraca) may be effective in patients with advanced pancreatic cancer who have a BRCA1/2 or PALB2 mutation (J Clin Oncol 2021 May 10 [Epub ahead of print]). Patients who received the PARP inhibitor following platinum-based chemotherapy in a phase II trial had a median progression-free survival (PFS) of 13.1 months and a median overall survival of 23.5 months.
  • Preliminary results announced by AstraZeneca/Daiichi Sankyo suggest that the TROP2-directed antibody–drug conjugate datopotamab deruxtecan (DS-1062) may be active in patients with metastatic triple-negative breast cancer (TNBC) who have received other therapies. In the phase I TROPION-PanTumor01 trial, five of 21 evaluable patients responded to the drug, and four more responses are awaiting confirmation; 11 patients experienced stable disease. Findings were presented at the 2021 European Society of Medical Oncology Breast Cancer Virtual Congress.
  • Genentech's BRAF inhibitor vemurafenib (Zelboraf) and anti-CD20 agent rituximab (Rituxan) may lead to durable responses in hairy-cell leukemia (N Engl J Med 2021;384:1810–23). In a phase II trial, the drug elicited complete responses in 26 of 30 patients with relapsed/refractory disease, and 17 of those patients were negative for minimal residual disease. The PFS rate was 78% at a median of 37 months, and 85% of patients who responded were relapse-free at a median follow-up of 34 months.
  • The launch of a translational research platform to study rare cancers was announced. The effort is a collaboration between The University of Texas MD Anderson Cancer Center in Houston and the Broad Institute of MIT and Harvard in Cambridge, MA. Its researchers aim to generate more than 100 rare cancer models linked to comprehensive molecular data that will be available to the research community.
  • African American women with TNBC may have a higher mortality rate than their white counterparts (JAMA Oncol 2021 May 13 [Epub ahead of print]). Researchers conducted a retrospective analysis of 23,123 women diagnosed with nonmetastatic TNBC between 2010 and 2015, 25.3% of whom were African American. They found that African American women had a 28% increased risk of death compared with white women, and that this disparity was in part due to lower rates of surgery and chemotherapy.
  • Dana-Farber Cancer Institute (DFCI) in Boston, MA, received a $50 million donation to study pancreatic cancer. The money will be used to purchase laboratory equipment for in-depth research on the biology of pancreatic tumors. The gift is from the Judith B. Hale, her son, Robert T. Hale Jr., and his wife, Karen Hale; the family has now contributed more than $80 million to DFCI.

April 30–May 6

  • The FDA granted accelerated approval to the PD-1 inhibitor pembrolizumab (Keytruda; Merck) plus trastuzumab (Herceptin; Genentech) and chemotherapy in patients newly diagnosed with certain HER2-positive gastric or gastroesophageal cancers. In the phase III KEYNOTE-811 trial, patients treated with the investigational combination had an overall response rate of 74%, compared with 52% in patients who received trastuzumab plus chemotherapy. In April, an FDA advisory committee recommended revoking accelerated approval of pembrolizumab monotherapy as a third-line option in these patients, citing little evidence of benefit and the upcoming first-line approval.
  • AstraZeneca/Daiichi Sankyo’s trastuzumab deruxtecan (Enhertu) may be effective in HER2-positive metastatic colorectal cancer (Lancet Oncol 2021 May 4 [Epub ahead of print]). In the phase II DESTINY-CRC01 trial, 53 patients had an objective response rate of 68% and a median progression-free survival of 6.9 months. A HER2-targeted antibody–drug conjugate, trastuzumab deruxtecan is FDA approved for certain HER2-positive breast and gastric cancers.
  • A deep learning algorithm may predict where cancers originate (Nature 2021 May 5 [Epub ahead of print]). During a test run of 6,500 cancers with known primary sites, the model identified the site of origin in 83% of cases and listed the correct diagnosis among its top three predictions in 96% of cases. Of 317 cancers with unknown primary sites for which a differential diagnosis had been assigned, the algorithm agreed with the pathologist in 61% of cases and had top-three agreement in 82% of cases.
  • Pfizer announced a pause in enrollment in the phase I MagnetisMM-3 trial of elranatamab (PF-06863135) in multiple myeloma due to three cases of peripheral neuropathy. The company has also halted a phase II trial of the drug while it provides additional safety information to the FDA. Elranatamab targets BCMA and CD3.
  • Parents and siblings of patients with colorectal polyps may have a higher risk of colorectal cancer (Br J Cancer 2021;373;n877). Researchers analyzed data from 68,060 patients with colorectal cancer and 333,753 matched controls. They found that 8.4% of patients with the disease had a first-degree relative with colorectal polyps, compared with 5.7% of healthy participants; the risk of colorectal cancer was even more pronounced in those who had at least two first-degree relatives with polyps, or a relative who developed polyps at a young age.
  • Researchers have developed a fluorescent imaging system based on the visual system of mantis shrimp to assist surgical oncologists as they operate (Sci Transl Med 2021;13:eaaw7067). The system, which consists of layers of silicon photodetectors and spectral filters stacked into a single chip, can detect multiple colors and near-infrared light. In mice with human prostate tumors, the system distinguished cancer cells from healthy tissue in 92% of cases; in 18 patients with breast cancer, it helped surgeons map lymph nodes close to tumors.

April 2021

April 23–29

  • The FDA's Oncologic Drugs Advisory Committee voted to maintain accelerated approvals for four of six immunotherapy indications that were under review. The favorable votes were for the use of pembrolizumab (Keytruda; Merck) in hepatocellular carcinoma and urothelial carcinoma, and atezolizumab (Tecentriq; Genentech) in triple-negative breast cancer and urothelial carcinoma; the committee voted against pembrolizumab to treat gastric cancer and nivolumab (Opdivo; Bristol Myers Squibb) to treat hepatocellular carcinoma. The FDA doesn’t need to follow the committee's recommendation, although it usually does so.
  • The FDA granted accelerated approval to loncastuximab tesirine-lpyl (Zynlonta; ADC Therapeutics) in patients with relapsed/refractory large B-cell lymphoma who have received at least two other therapies. The approval was based on the phase II LOTIS-2 trial, in which patients had an overall response rate of 48.3% and a median duration of response of 10.3 months. The agent is a CD19-targeting antibody–drug conjugate.
  • The agency also announced it plans to ban menthol cigarettes and all flavored cigars within the next year. "Banning menthol—the last allowable flavor—in cigarettes and banning all flavors in cigars will help save lives, particularly among those disproportionately affected by these deadly products," said Acting FDA Commissioner Janet Woodcock, MD, noting higher rates of use among communities of color, people with low income, and LGBTQ+ individuals.
  • The FDA issued a Notice of Noncompliance to Acceleron Pharma for not reporting trial results to clinicaltrials.gov. The company now has 30 days to upload findings to the site, after which it could be fined up to $10,000 per day. The notice is the first issued by the FDA to enforce a Health and Human Services Department rule finalized in 2016, although the agency has sent more than 40 warnings to other companies.
  • Young men are less likely to receive the human papillomavirus vaccine than young women, researchers reported (JAMA 2021;325:1673–4). Researchers reviewed vaccination data for 18- to 21-year-olds gathered by the National Health Interview Survey from 2010 to 2018. They found that, overall, 42% of females and 16% of males received at least one dose of the vaccine; in 2010, 32% of females and 2% of males received at least one dose, compared with 55% and 34%, respectively, in 2018.
  • Galera announced that avasopasem (GC4419) may improve the effectiveness of stereotactic body radiation in patients with locally advanced pancreatic cancer. In a phase I/II trial, patients treated with the agent plus radiotherapy had a median overall survival of 20.1 months and a response rate of 29%, compared with 10.9 months and 11% in patients who received radiotherapy alone. Avasopasem is a dismutase mimetic designed to convert superoxide into hydrogen peroxide and oxygen, thus protecting normal tissue from damage during radiotherapy.

April 16–22

  • The FDA granted accelerated approval to dostarlimab-gxly (Jemperli; GlaxoSmithKline) for patients with mismatch repair–deficient recurrent or advanced endometrial cancer who have already received chemotherapy. The approval of the PD-1 inhibitor was based on the single-arm GARNET trial, in which patients had an overall response rate of 42.3%, and 93.3% of patients responded for at least 6 months.
  • Bristol Myers Squibb announced that the FDA approved nivolumab (Opdivo) plus chemotherapy for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma—regardless of PD-L1 expression. The PD-1 inhibitor’s approval was based on the CHECKMATE-649 trial, in which patients treated with the combination had a median progression-free survival (PFS) of 7.7 months and a median overall survival (OS) of 14.4 months, compared with 6 months and 11.1 months, respectively, in patients who received chemotherapy alone.
  • The antibody–drug conjugate sacituzumab govitecan (Trodelvy; Immunomedics) may be effective in patients with relapsed/refractory triple-negative breast cancer (N Engl J Med 2021;384:1529–41). In the phase III ASCENT trial, patients treated with the agent had a median PFS of 5.6 months and a median OS of 12.1 months, compared with 1.7 months and 6.7 months, respectively, in patients who received chemotherapy. The FDA recently approved sacituzumab govitecan to treat these patients.
  • According to results of the ongoing phase I/II AUGMENT-101 trial, the menin inhibitor SNDX-5613 (Syndax) may be effective in patients with MLL rearranged or NPM1 mutant relapsed/refractory acute leukemias. In the trial, 15 of 31 evaluable patients responded to the drug, and 10 responders were minimal residual disease–negative; responses were seen in 13 of 24 patients with MLL rearranged disease.
  • A group of public and private cancer organizations announced the formation of a Multi-Cancer Early Detection Consortium. The consortium will evaluate the clinical and public health value of new cancer detection technologies and establish standards for using such technologies in routine medical care. More than 35 organizations have joined so far; founding members include Dana-Farber Cancer Institute in Boston, MA, Stand Up To Cancer, and Grail, among others.
  • Researchers launched the DiRECT study to investigate racial differences in response to immune checkpoint inhibitors. Led by New York’s Roswell Park Comprehensive Cancer Center in Buffalo and Wilmot Cancer Institute at the University of Rochester Medical Center, the study aims to enroll 600 Black patients and 1,200 white patients of European ancestry treated with immunotherapy. The project is supported by a 2-year, $2.08 million NCI grant.
  • Janssen Pharmaceuticals will not pursue FDA approval of the androgen receptor inhibitor apalutamide (Erleada) plus abiraterone acetate (Zytiga) and prednisone in patients with metastatic castration-resistant prostate cancer who have not received chemotherapy. The decision came after the triplet failed to improve OS compared with abiraterone acetate and prednisone alone in the phase III ACIS trial.

April 9–15
This week: Special content from the AACR Annual Meeting 2021 and other news

  • NCI Director Norman "Ned" Sharpless told attendees of the American Association for Cancer Research (AACR) Annual Meeting 2021 that progress must speed up dramatically. To cut the cancer mortality rate in half from its peak in the early 1990s, "will require a considerable acceleration of what we’ve been able to achieve in the last few decades," he said. At the current rate of 2.2% per year, it would take until 2040 to reach that goal—"that’s too long… Using all of our many tools of prevention and screening and new therapies, I think we can get there by 2026—that’s 5 years from now. This would require an average reduction in cancer mortality of about 4% per year, which is considerably faster than the rate of decline we’ve ever done before."
  • In a high-level outline of its budget priorities for fiscal year 2022 released on April 9, the Biden Administration proposed a total increase of $9 billion for the NIH. Of that, $2.5 billion would be distributed to the NIH’s various institutes, of which the NCI is the largest, Sharpless reported. If approved by Congress, "that would translate into a substantial increase in the NCI’s budget for FY2022. This would be key to allowing the NCI to continue to increase paylines and success rates for grant applications."
  • Aiming to cure major diseases, including cancer and diabetes, the Biden Administration proposed creating a $6.5 billion medical research agency that would be "housed" within the NIH. The Advanced Research Projects Authority for Health would be modeled after the Defense Advanced Research Projects Agency, wherein funding decisions are made by program managers rather than peer reviewers, and projects receive milestone-driven payments instead of multiyear grants.
  • During the AACR meeting, Melissa Davis, PhD, of Weill Cornell Medical College in New York, NY, discussed how a lack of genomic data from diverse populations can lead to disparities in cancer research. "Just about any population that is of non-European descent has a higher rate of reporting back on a mutation panel a variant of unknown significance," she said. These panels are used to determine eligibility for trials, she added, so "if their mutations are undefined and therefore by definition unknown and unactionable, this a systematic exclusion of these individuals for their access to trials."
  • The director of the Cold Spring Harbor Laboratory Cancer Center in New York, David Tuveson, MD, PhD, was inaugurated as president of the AACR on April 12, succeeding Antoni Ribas, MD, PhD, of the University of California, Los Angeles, Jonsson Comprehensive Cancer Center. Lisa Coussens, PhD, of the Knight Cancer Institute at Oregon Health & Science University in Portland, will become the organization’s president following Tuveson’s 1-year term.
  • At the AACR meeting, Eric Klein, MD, of Ohio’s Cleveland Clinic reported data from a prospective study on Galleri, GRAIL’s multicancer early detection test. Researchers assessed Galleri, which relies on sequencing of methylation regions in circulating cell-free DNA to detect malignancies, on 2,823 patients with cancer and 1,254 healthy people. The assay had a specificity of 99.5% and a sensitivity of 51.5% across cancer types and stages; sensitivity increased with cancer stage. Among patients who tested positive for cancer, Galleri accurately determined the tissue of origin in 88.7% of cases. "These data support the foundation for population-scale clinical implementation of this test," Klein concluded.
  • Engineered natural killer (NK) cells can target specific antigens via expression of chimeric antigen receptors (CAR). As an alternative approach to endow NK cells with CAR-like activity, Katayoun Rezvani, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, reported the generation of cord blood–derived NK cells precomplexed prior to infusion with AFM13 (Affimed), a bispecific innate cell engager that binds CD16 on NK cells and CD30 on tumor cells. Preliminary results from a phase I trial indicate that adoptive transfer of AFM13-complexed CAR-like NK cells shows antitumor activity with minimal toxicity in patients with relapsed/refractory CD30+ Hodgkin lymphoma.
  • Tumor heterogeneity can make it difficult to determine which tumors are immunologically "hot" and thus more likely to respond to immunotherapy. Elisabeth De Vries, MD, PhD, and colleagues at the University Medical Center Groningen in the Netherlands explored whole-body PET imaging and reported that tumor uptake of radiolabeled PD-1 antibodies is associated with prolonged progression-free and overall survival. "Whole body information about what’s happening at the tumor and normal tissue level might provide insights into what’s happening during the complex processes induced by immunotherapy," she told AACR meeting attendees.
  • Also at the AACR meeting, Ross Levine, MD, of Memorial Sloan Kettering Cancer Center in New York, NY, outlined studies demonstrating the power of single-cell sequencing technology to precisely identify the timing of mutations and define clonal trajectories. Follow-up studies have shown that clonal genotypes are associated with distinct immunophenotypes, he said, and advances in in vivo modeling and multi-omics single-cell sequencing will provide insight into the mechanisms underlying evolutionary mutational trajectories and enable elucidation of the biological underpinnings of clonal hematopoiesis.
  • Michel Sadelain, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, NY, described several advances in chimeric antigen receptor (CAR) T-cell therapy that might improve its efficacy—modulation of transcriptional regulation, signaling calibration, and epigenetic enhancement. He also introduced a novel CAR design called HIT receptor and demonstrated its greater antigen sensitivity compared with "traditional" CAR T-cell therapy.
  • The 4-1BB (CD137)/HER2 bispecific cinrebafusp alfa (PRS-343; Pieris) may be active in patients with HER2-expressing cancers who have previously received multiple therapies. In a phase I trial presented at the AACR meeting, five of 42 evaluable patients responded to the therapy, and 17 more patients experienced stable disease; two of the responses—including one complete response—were in eight patients treated at the highest dose level. The agent increased CD8+ T cells, NK cells, and cytotoxic activity in the tumor microenvironment.
  • Researchers described the discovery of INCB89550, a PD1/PD-L1 inhibitor at the AACR meeting that is being tested in clinical trials. Using high-throughput screening, the team initially identified a compound that exhibited dose-dependent inhibition of PD-1–PD-L1 interactions. Analysis of the amino acid residues critical for drug activity revealed that the inhibitor blocked binding by interacting with PD-L1 directly at the PD-1–PD-L1 binding interface—a rare occurrence because this interface is largely flat and lacks a defined binding pocket. The researchers then used rational, structure-guided design of improved inhibitors derived from the initial hit to identify INCB086550 as a candidate for clinical development.
  • Also at the AACR meeting, researchers reported promising preclinical results for the targeted thorium conjugate HER2-TTC (BAY2701439; Bayer). The agent consists of a radioactive thorium isotope bound by a chelator that is covalently linked to a HER2 antibody. It kills HER2-expressing cells and neighboring cells by delivering alpha radiation that induces DNA damage—for which there is no known resistance mechanism. Preclinical results suggest that HER2-TTC may have anti-tumor activity in cancers with low levels of HER2 expression, as well as those that are resistant to other HER2-targeted agents. The agent is now being tested in a phase I trial of HER2-expressing malignancies.

  • In other news:

  • The FDA authorized the marketing of the artificial intelligence device GI Genius (Cosmo Artificial Intelligence), which assists clinicians in detecting lesions during a colonoscopy. In a prospective trial of patients with adenoma or carcinoma, the technology identified lesions in 55.1% of cases, compared with a 42% detection rate for colonoscopy alone. The device, which uses a machine learning algorithm, attaches to an endoscope and identifies regions of interest in the colon, alerting clinicians to take a closer look.
  • The agency also granted accelerated approval to sacituzumab govitecan (Trodelvy; Immunomedics), an antibody–drug conjugate, for patients with locally advanced or metastatic urothelial cancer who have received chemotherapy and a PD1/PD-L1 inhibitor. The approval was based on the phase II TROPHY trial, in which patients had an objective response rate of 27.7% and a median duration of response of 7.2 months.
  • GlaxoSmithKline (GSK) halted the phase II INDUCE-3 trial testing feladilimab, an inducible T-cell co-stimulatory agonist, plus pembrolizumab (Keytruda; Merck) in head and neck cancer based on the recommendation of an independent data monitoring committee. The company will also discontinue the phase II INDUCE-4 trial assessing feladilimab plus pembrolizumab and chemotherapy in head and neck cancer. GSK did not share details of the committee’s recommendation.

April 2–8

  • Daiichi Sankyo announced it will invest $13.6 billion in new cancer treatments through March 2026, an investment that represents a nearly 70% increase over the previous 5-year period. The company aims to expand the uses for the HER2-targeted antibody–drug conjugate (ADC) trastuzumab deruxtecan (Enhertu), jointly developed with AstraZeneca, beyond breast and gastrointestinal cancers. Also, the company plans to develop other ADCs, including TROP2- and HER3-targeting agents.
  • Researchers suggested that eligibility criteria for some cancer clinical trials could be expanded (Nature 2021 Apr 7 [Epub ahead of print]). They used an artificial intelligence tool called Trial Pathfinder to emulate clinical trials based on electronic health records of 61,094 patients with advanced non–small cell lung cancer. When they broadened enrollment criteria for these hypothetical trials, they found that the pool of eligible patients more than doubled on average, while overall survival (OS) decreased minimally.
  • The FDA upgraded sacituzumab govitecan-hziy’s (Trodelvy; Gilead) accelerated approval to a full approval in patients with locally advanced or metastatic triple-negative breast cancer who aren’t eligible for surgery and have already received at least two therapies. The decision was based on the phase III ASCENT trial, in which the agent led to a median progression-free survival of 4.8 months and a median OS of 11.8 months, compared with 1.7 months and 6.9 months, respectively, in patients who received chemotherapy. Sacituzumab govitecan-hziy consists of a monoclonal antibody against human trophoblast cell-surface antigen 2 conjugated to the topoisomerase I inhibitor SN-38.
  • The agency also approved a biweekly dosing regimen for the EGFR inhibitor cetuximab (Erbitux; ImClone) in patients with EGFR-mutant colorectal cancer or head and neck cancer. The approval was based on pharmacokinetic and real-world data suggesting that patients derive a similar benefit whether they are treated with the drug weekly or receive a larger dose every 2 weeks.
  • Researchers projected that the landscape of cancer incidence and mortality in the United States will change considerably by 2040 (JAMA Network Open 2021;4:e214708). Notably, melanoma incidence will increase, whereas prostate cancer incidence will drop. Additionally, there will be more deaths from pancreatic and liver cancers and fewer deaths from breast cancer. Estimates were made by combining data from the Surveillance, Epidemiology, and End Results Program with projections from the U.S. Census Bureau.

March 2021

March 26–April 1

  • The Federal Trade Commission will seek to stop Illumina’s $7.1 billion acquisition of Grail. The government agency claims that the deal will inhibit the market for blood-based cancer detection tests because Illumina is the only provider of DNA sequencing for such tests. Grail was founded by Illumina in 2016 and later became a stand-alone company.
  • The FDA approved idecabtagene vicleucel (ide-cel, Abecma; Bristol Myers Squibb) for patients with relapsed/refractory multiple myeloma who have already received at least four therapies. In the phase III KarMMA trial, the agent elicited an overall response rate of 72% and a median duration of response of 11 months. Idecabtagene vicleucel is a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen; it is the first CAR T-cell therapy to be approved in multiple myeloma.
  • The agency also approved isatuximab-irfc (Sarclisa; Sanofi) plus carfilzomib (Kyprolis; Amgen) and dexamethasone in relapsed/refractory multiple myeloma. The approval was based on positive results in the phase III IKEMA trial: Patients treated with the triplet did not reach median progression-free survival, compared with 20.3 months in those who received carfilzomib plus dexamethasone. The approval is the first for isatuximab-irfc, a CD38-directed cytolytic antibody.
  • Jazz Pharmaceuticals announced that the FDA expanded the indication for daunorubicin and cytarabine (Vyxeos) to include children age 1 and older newly diagnosed with therapy-related acute myeloid leukemia (AML) or AML with myelodysplasia-related changes. The approval was supported by two single-arm trials, AAML 1421 and CPX-MA-1201, in which there were no age-related differences in safety. The agent, a combination of a nucleoside metabolic inhibitor and an anthracycline topoisomerase inhibitor, was approved for adults with AML in 2017.
  • Adjuvant nivolumab (Opdivo; Bristol Myers Squibb) may be effective in esophageal and gastroesophageal junction cancer (N Engl J Med 2021;384:1191–203). In the phase III CheckMate-557 trial, patients treated with the PD-1 inhibitor had a median disease-free survival of 22.4 months compared with 11 months in those who received a placebo.
  • A survey conducted by the American Society for Radiation Oncology found that the COVID-19 pandemic may be causing cancers to be diagnosed at later stages. Sixty-six percent of radiation oncologists said patients are being diagnosed with more advanced cancers than prior to the pandemic, and 73% said patients at their practices are not receiving cancer screenings. Additionally, 66% said patients with cancer have experienced an interruption in radiation therapy.

March 19–25

  • The FDA approved the PD-1 inhibitor pembrolizumab (Keytruda; Merck) plus chemotherapy in patients newly diagnosed with locally advanced or metastatic esophageal junction carcinoma who are not eligible for surgery or chemoradiation. The approval was based on the phase III KEYNOTE-590 trial, in which patients treated with the combination had a median progression-free survival (PFS) of 6.3 months and a median overall survival (OS) of 12.4 months, compared with 5.8 months and 9.8 months, respectively, in patients who received only chemotherapy.
  • Pembrolizumab plus the VEGF inhibitor lenvatinib (Lenvima; Merck) may improve survival in advanced, metastatic, or recurrent endometrial cancer, according to findings presented at the Society of Gynecologic Oncology 2021 Annual Meeting on Women’s Cancer, held virtually March 19–25. In the phase III KEYNOTE-775/Study 309 trial, patients treated with the combination had a median PFS of 7.2 months and a median OS of 18.3 months, compared with 3.8 months and 11.4 months, respectively, in patients who received standard chemotherapy.
  • Novartis announced that the radionuclide 177Lu-PSMA-617 may be effective in patients with metastatic castration-resistant prostate cancer that expresses prostate-specific membrane antigen. In the phase III VISION trial, the agent extended OS and radiographic PFS compared with standard chemotherapy, although the company did not share any data. In a phase II trial, the drug led to a higher objective response rate and prostate-specific antigen response than chemotherapy (The Lancet 2021;397:797–804).
  • Researchers from the COVID-19 and Cancer Consortium reported that Black and Hispanic patients tend to develop more severe COVID-19 infections than white patients (Ann Oncol 2021 Mar 18 [Epub ahead of print]). That conclusion was based on data from 4,966 patients with cancer who developed COVID-19 infections between March and November 2020. Other risk factors associated with more severe COVID-19 included older age, obesity, being male, and comorbidities.
  • Stand Up To Cancer (SU2C) awarded $6 million to a team studying health equity in cancer research. The SU2C Health Equity Breakthrough Team will address underrepresentation of Black and indigenous populations, and people of color in breast, prostate, and liver cancer trials by working with community organizations, training scientists and doctors, and exploring better ways to educate these patients. The team is part of SU2C’s Health Equity Initiative, which launched in January 2020.

March 12–18

  • Sanofi and Regeneron announced that a phase III trial testing cemiplimab (Libtayo) in recurrent or metastatic cervical cancer will be stopped early due to positive results. The decision was made because patients treated with the agent experienced a statistically significant improvement in median overall survival compared with those who received chemotherapy: 12 months versus 8.5 months, respectively. A PD-1 inhibitor, cemiplimab is FDA approved for certain forms of basal cell carcinoma and non–small cell lung cancer.
  • Bintrafusp alfa (GlaxoSmithKline/Merck KGaA) may not be effective as a second-line therapy for patients with locally advanced or metastatic biliary tract cancer (BTC) who have received platinum-based chemotherapy. In a phase II trial, the agent elicited an objective response rate of 10.1%, which failed to meet the predefined threshold for efficacy. A bifunctional fusion protein that blocks TGFβ and PD-L1, bintrafusp alfa will continue to be tested in combination with chemotherapy in BTC.
  • Socioeconomically disadvantaged patients enrolled in cancer clinical trials may fare worse than their more affluent counterparts despite receiving high-quality care during the trials (J Clin Oncol 2021 Mar 17 [Epub ahead of print]). Researchers analyzed data from 41,109 patients with cancer enrolled in 55 phase II and III trials between 1985 and 2012. They found that patients from the poorest neighborhoods had a 28% increased risk of death compared with those from the most affluent areas.
  • A survey revealed that disposable electronic cigarettes (e-cigarettes) are becoming increasingly popular among kids (NEJM 2021 Mar 16 [Epub ahead of print]). Researchers analyzed responses from middle school and high school students gathered during 2019 and 2020. They found that among current e-cigarette users, the use of disposable devices increased from 3% to 15.2% for middle schoolers and from 2.4% to 26.5% for high schoolers.
  • A group of 47 UK charities warned that without government action, the COVID-19 pandemic could cause the UK’s cancer death rate to increase for the first time in decades. The warning highlights delays in cancer screening, diagnosis, and treatment during the pandemic, as well as disruptions to clinical trials. It urges governments to take steps such as directing resources into clearing the backlog of cancer cases, encouraging people with signs of cancer to seek care, and expanding the cancer workforce.
  • Five research teams were awarded Cancer Research UK–Children with Cancer UK Innovation Awards. Each team will receive up to $1.4 million over the next 3 years. With the funding, researchers will tackle projects such as analyzing inherited risk for solid cancers, developing targeted immunotherapy for leukemia in infants, and creating an atlas of rhabdomyosarcoma cases.

March 5–11

  • The FDA approved tivozanib (Fotivda; AVEO Oncology) for patients with relapsed/refractory advanced renal cell carcinoma who have received at least two prior therapies. The approval was based on the phase III TIVO-3 trial, in which patients treated with the agent had a median progression-free survival of 5.6 months and a median overall survival (OS) of 16.4 months, compared with 3.9 months and 19.2 months for patients who received sorafenib. The approval is the first for tivozanib, a VEGF tyrosine kinase inhibitor.
  • The agency also approved axicabtagene ciloleucel (Yescarta; Kite Pharma) in patients with relapsed/refractory follicular lymphoma who have received at least two prior therapies. The approval is based on the phase II ZUMA-5 trial, in which 91% of patients responded to the drug and 74% of patients were in remission at 18 months. A chimeric antigen receptor T-cell therapy, axicabtagene ciloleucel was previously approved for certain types of large B-cell lymphoma.
  • Following a review of recent research, the U.S. Preventive Services Task Force released a final guideline that expands the criteria for lung cancer screening (JAMA 2021;325;962–70). The document calls for screening adults ages 50 to 80 who have a 20 pack-year smoking history and who currently smoke or have quit within the past 15 years. Previously, the agency recommended that screening start at age 55 for people with a 30 pack-year smoking history.
  • Roche will stop marketing the PD-L1 inhibitor atezolizumab (Tecentriq) in the United States for patients with metastatic urothelial carcinoma who have received platinum-based chemotherapy. The decision was made in consultation with the FDA after the agent failed to meet its OS endpoint in the phase III IMvigor211 trial. The FDA had granted atezolizumab accelerated approval in 2016 based on results of the phase II IMvigor210 trial. In late April, the FDA Oncologic Drugs Advisory Committee will convene a meeting to review six other accelerated approvals for PD-1/PD-L1 agents.
  • The Bruton tyrosine kinase (BTK) inhibitor pirtobrutinib (LOXO-305; Loxo Oncology) may be effective in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL), mantle cell lymphoma, and other non-Hodgkin lymphomas (Lancet 2021;397:892–901). In the phase I/II BRUIN trial, the agent elicited overall response rates (ORR) ranging from 52% to 71%, depending on the disease; 121 patients with CLL or SLL previously treated with a BTK inhibitor had an ORR of 67%.
  • A study suggests that the globalization of cancer clinical trials may contribute to racial disparities in enrollment (Cancer 2021 Mar 8 [Epub ahead of print]). Researchers analyzed 49 international trials that led to 35 drug approvals by the FDA between 2015 and 2018. They found that, overall, Black patients accounted for only 2.5% of enrollment, and trials with more patients enrolled outside the United States had fewer Black participants.
  • Based on findings from the phase III CANOPY-2 trial, Novartis announced that adding the IL1β inhibitor canakinumab (ACZ885) to chemotherapy may not improve OS of patients with locally advanced or metastatic non–small cell lung cancer who have received treatment. Canakinumab will continue to be tested as a first-line and adjuvant therapy in the phase III CANOPY-1 and CANOPY-A trials.

February 26–March 4

  • Amgen announced it will acquire Five Prime Therapeutics for $1.9 billion. In the deal, Amgen will gain Five Prime’s anti-FGFR2b agent bemarituzumab (FPA144), which is in clinical testing for patients with advanced gastric cancer and FGFR2b mutations. In the phase II FIGHT trial, bemarituzumab plus chemotherapy led to longer overall and progression-free survival than chemotherapy alone.
  • The FDA approved the ALK inhibitor lorlatinib (Lorbrena; Pfizer) in patients newly diagnosed with metastatic non–small cell lung cancer (NSCLC) who have ALK mutations. The approval was based on the phase III CROWN trial, in which the agent reduced the risk of disease progression or death by 72% compared with crizotinib (Xalkori; Pfizer). The agency also converted lorlatinib’s 2018 accelerated approval for previously treated ALK-positive NSCLC into a full approval.
  • The FDA also granted accelerated approval to melphalan flufenamide (Pepaxto; Oncopeptides AB) plus dexamethasone in patients with relapsed/refractory multiple myeloma who have received at least four prior therapies. The decision was based on the phase II HORIZON trial, in which the drug elicited an overall response rate of 23.7%, and patients responded for a median of 4.2 months. The approval is the first for melphalan flufenamide, a peptide–drug conjugate.
  • Researchers reported that blinatumomab may be effective in children with high-risk relapsed B-cell acute lymphoblastic leukemia (JAMA 2020;325:843–54). In a phase III trial, 31% of patients treated with blinatumomab experienced relapse, death, or a second malignancy after a median of 22.4 months, compared with 57% of those who received consolidation chemotherapy. Blinatumomab is a bispecific antibody that targets CD3 and CD19.
  • An analysis revealed that the COVID-19 pandemic may be disrupting pediatric cancer care worldwide (Lancet Child Adolesc Health 2021 Mar 3 [Epub ahead of print]). Researchers surveyed pediatric oncology providers at 213 institutions in 79 countries between June 22 and August 21, 2020. Overall, 43% of centers reported a decrease in newly diagnosed pediatric cancers and 34% reported an increase in "treatment abandonment," defined as a failure to start treatment or a delay in care of 4 weeks or longer.
  • Merck announced it will stop U.S. marketing of pembrolizumab (Keytruda) for previously treated metastatic small cell lung cancer. The decision came after the agent failed to improve overall survival in the phase III KEYNOTE-604 trial. Previously, the FDA granted the PD-L1 inhibitor accelerated approval for this indication based on encouraging results in the early-phase KEYNOTE-158 and KEYNOTE-028 trials.

February 2020

February 19–25

  • The FDA approved the PD-1 inhibitor cemiplimab-rwlc (Libtayo; Regeneron/Sanofi) as a first-line treatment for patients with advanced non–small cell lung cancer and high PD-L1 expression. The approval was based on the phase III EMPOWER-Lung 1 trial, in which patients treated with the agent had a median overall survival (OS) of 22.1 months and a median progression-free survival (PFS) of 6.2 months, compared with 14.3 months and 5.6 months, respectively, in patients who received chemotherapy.
  • Idecabtagene vicleucel (ide-cel/bb2121; Bluebird Bio/Celgene) may be effective in patients with relapsed/refractory multiple myeloma (N Engl J Med 2021 Feb 25 [Epub ahead of print]). In the phase II KarMMa trial, 128 patients had an overall response rate of 73% and a median PFS of 8.8 months. Idecabtagene vicleucel is an autologous chimeric antigen receptor T-cell therapy that targets B-cell maturation antigen.
  • The launch of a new foundation called Break Through Cancer was announced. The foundation will bring together cancer scientists at five institutions: The Koch Institute for Integrative Cancer Research at MIT in Cambridge, MA, the Dana-Farber Cancer Institute in Boston, MA, Memorial Sloan Kettering Cancer Center in New York, NY, the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, MD, and The University of Texas MD Anderson Cancer Center in Houston. Multidisciplinary teams will conduct translational research on difficult-to-treat malignancies such as pancreatic cancer, ovarian cancer, glioblastoma, and acute myeloid leukemia.
  • AstraZeneca will stop marketing the PD-L1 inhibitor durvalumab (Imfinzi) for locally advanced or metastatic bladder cancer in the United States. The FDA previously granted the agent an accelerated approval based on encouraging results in the phase I/II Study 1108 trial. The agent has since failed to meet its primary endpoint of improving OS compared with standard chemotherapy in the phase III DANUBE trial, prompting the decision.
  • The Epidemiology of Young Lung Cancer study launched to investigate the underlying causes of lung cancer in patients diagnosed before age 40. Researchers aim to gather medical, environmental, demographic, and lifestyle data from 250 patients with early-onset lung cancer and use this information to identify potential risk factors. The effort is a collaboration between the Addario Lung Cancer Medical Institute and the GO2 Foundation for Lung Cancer.
  • "Once we beat COVID, we’re going to do everything we can to end cancer as we know it," President Joe Biden said during a speech he gave after a tour of one of Pfizer’s COVID-19 vaccine manufacturing sites. Biden added that the President’s Council of Advisors on Science and Technology and the Office of Science and Technology Policy are developing an “advanced research effort on cancer and other diseases.” While serving as vice president, Biden led the White House’s Cancer Moonshot initiative.

February 12–18

  • Lenvatinib (Lenvima; Eisai) plus pembrolizumab (Keytruda; Merck) or everolimus (Afinitor; Novartis) may be effective in patients with advanced renal cell carcinoma. In the phase III CLEAR trial, patients treated with the pembrolizumab combination had a median progression-free survival (PFS) of 23.9 months and an objective response rate of 71%, compared with 14.7 months and 53.5% in patients who received the everolimus combination, and 9.2 months and 36.1%, respectively, in those who received standard sunitinib (Sutent; Pfizer). Findings were presented at the 2021 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium, held virtually February 11–13, and simultaneously published (N Engl J Med 2021 Feb 13 [Epub ahead of print]).
  • Also presented at ASCO GU and published concurrently, researchers reported that the Nectin4-directed antibody–drug conjugate enfortumab vedotin (Seattle Genetics/Astellas) may extend survival for patients with advanced urothelial carcinoma who have already received chemotherapy and a PD-1–PD-L1 inhibitor (N Engl J Med 2021 Feb 12 [Epub ahead of print]). In the phase III EV-301 trial, patients treated with the agent had a median overall survival (OS) of about 12.9 months and a median PFS of 5.6 months, compared with nearly 9 months and 3.7 months, respectively, in patients who received standard chemotherapy. /li>
  • The tyrosine kinase inhibitor cabozantinib (Cabometyx; Exelixis) may be superior to sunitinib in patients with metastatic papillary renal cell carcinoma, according to findings reported at ASCO GU and concurrently published (Lancet 2021;397:P695–703). In a phase II trial, cabozantinib led to a response rate of 23% and a median PFS of 9 months, compared with 4% and 5.6 months for sunitinib.
  • Regeneron/Sanofi’s PD-1 inhibitor cemiplimab-rwlc may improve survival for patients newly diagnosed with advanced non–small cell lung cancer and high PD-L1 expression (Lancet 2021;397:P592¬–604). In the phase III EMPOWER-Lung 1 trial, patients treated with the agent did not reach median OS and had a median PFS of 8.2 months, compared with 14.2 months and 5.7 months, respectively, in patients who received standard chemotherapy.
  • The FDA approved the CDK4/6 inhibitor trilaciclib (Cosela; G1 Therapeutics) to protect bone marrow function and reduce the risk of severe neutropenia in patients receiving chemotherapy for extensive-stage small cell lung cancer. The approval was based on pooled findings from three randomized trials in which 11.4% of patients treated with the agent developed severe neutropenia during chemotherapy, compared with 52.9% of patients who received a placebo.
  • U.S. cancer centers and organizations issued a letter urging the Biden administration to prioritize COVID-19 vaccines for patients with cancer and survivors of cancer. "There is mounting evidence that patients with cancer are at increased risk of severe illness and death if they are infected with the virus," the letter states, adding that certain cancer survivors also have a higher risk of infection and death. The document was signed by more than 130 organizations, including the American Association for Cancer Research and the European Society for Medical Oncology.
  • The Leukemia & Lymphoma Society (LLS) launched the LLS National Patient Registry to gather data on patients with blood cancer who have been vaccinated against COVID-19, as well as those who have tested positive for the virus. Researchers aim to understand how patients with hematologic malignancies respond to the vaccine based on their type of cancer and any treatment they are receiving. Patients can join at www.lls.org.

February 5–11

  • Adjuvant nivolumab may be effective in patients with muscle-invasive urothelial carcinoma, according to findings presented at the 2021 American Society of Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium, held virtually February 11–13. In the phase III CheckMate 274 trial, patients treated with the PD-1 inhibitor after surgery had a median disease-free survival of 21 months, compared with 10.9 months in patients who received a placebo.
  • Also at ASCO GU, researchers reported that a decrease in prostate-specific antigen (PSA) testing has led to an increase in metastatic disease at diagnosis. Investigators analyzed data on PSA screening and metastatic prostate cancer in each U.S. state between 2008 and 2016. They found that the average percentage of eligible men screened for PSA overall decreased from 61.8% to 50.5%, while the incidence of metastatic disease at diagnosis increased from 6.4 to 9 cases per 100,000 men—and bigger drops in PSA screening were associated with larger increases in metastatic prostate cancer diagnoses.
  • The FDA approved lisocabtagene maraleucel (Breyanzi; Bristol Myers Squibb) in adults with relapsed/refractory large B-cell lymphoma who previously received at least two other therapies. The approval was based on the TRANSCEND NHL 001 trial, in which 192 patients had an overall response rate of 73% and a complete response rate of 54%. The approval is the first for lisocabtagene maraleucel, a chimeric antigen receptor T-cell therapy that targets CD19.
  • The FDA approved the PD-1 inhibitor cemiplimab-rwlc (Libtayo; Regeneron/Sanofi) in patients with locally advanced basal cell carcinoma who have already received a hedgehog pathway inhibitor (HHI), or who aren’t eligible for an HHI. The agency also granted accelerated approval to the drug for use in patients with metastatic disease. The approvals were based on Study 1620, in which patients with advanced disease had an objective response rate of 29%, and those with metastatic disease had an objective response rate of 21%.
  • The agency also granted accelerated approval to the PI3Kδ inhibitor umbralisib (Ukoniq; TG Therapeutics) in patients with relapsed/refractory marginal zone lymphoma (MZL) who received at least one prior anti-CD20 therapy, as well as in patients with relapsed/refractory follicular lymphoma (FL) who received at least three prior therapies. In the phase II UNITY-NHL trial, the agent elicited responses in 49% and 43% of patients with MZL and FL, respectively.
  • The FDA Oncologic Drugs Advisory Committee voted 10 to 0 against pembrolizumab (Keytruda; Merck) as a neoadjuvant therapy for high-risk triple-negative breast cancer. The committee concluded that the 7.5% improvement in pathologic complete response seen in the phase III KEYNOTE-522 trial is not large enough to indicate a clinical benefit, and more definitive findings are needed. The trial will continue to amass data on event-free survival and overall survival (OS).
  • AstraZeneca announced that durvalumab (Imfinzi) may not extend survival in patients with recurrent or metastatic head and neck squamous cell carcinoma and high PD-L1 expression. In the phase III KESTREL trial, the agent did not improve OS compared with standard chemotherapy. A PD-L1 inhibitor, durvalumab is FDA approved for certain forms of lung and bladder cancer.

January 29–February 4

  • At the American Association for Cancer Research (AACR) Virtual Meeting: COVID-19 and Cancer, held February 3–5, researchers reported that patients with lymphoma treated with B cell–depleting therapies may have poor outcomes if they develop severe COVID-19. Researchers evaluated 111 patients with lymphoma admitted to the hospital with severe COVID-19 infections, 63 of whom had received B cell–depleting therapies within the past year. These patients were almost twice as likely to stay in the hospital for more than 30 days than those who had received other therapies—and they were more than twice as likely to die.
  • Also at the AACR COVID-19 and Cancer meeting, researchers highlighted the financial burden of the COVID-19 pandemic on people who survive cancer. The team analyzed data from 10,760 U.S. adults during the pandemic, including 854 people who had been diagnosed with cancer. They found that 18% of cancer survivors experienced financial hardship during the pandemic; younger adults and those insured through Medicaid or living in rural areas were more likely to experience money troubles than those who had not been diagnosed with cancer.
  • A pair of papers revealed that fecal microbiota transplant (FMT) may improve immunotherapy responses in patients with melanoma. In one study, researchers transplanted fecal microbiota from seven immunotherapy responders to 16 patients with PD-1–refractory melanoma (Science 2021;6529:595–602). After transplant, six of the recipients responded to pembrolizumab (Keytruda; Merck). The second paper reported on a phase I trial in which three of 10 patients who had progressed on immunotherapy responded to a PD-1 inhibitor after FMT (Science 2021;6529:602–9).
  • People who survive cancer are more likely to have underlying medical conditions linked to severe COVID-19 than those in the general population (J Natl Cancer Inst 2021 Feb 3 [Epub ahead of print]). Researchers analyzed data from 6,411 people who had had cancer and 77,748 people without a history of cancer. They found that 56.4% of survivors had at least one medical condition associated with an increased risk of severe COVID-19, such as heart disease and diabetes, compared with 41.6% of people who hadn’t had cancer.
  • The FDA granted accelerated approval to tepotinib (Tepmetko; EMD Serono) in patients with metastatic non–small cell lung cancer with MET exon 14 skipping mutations. The approval was based on the phase II VISION trial, in which 69 newly diagnosed patients had an overall response rate (ORR) of 43% and a median duration of response (DoR) of 10.8 months; 83 patients who had received prior therapies had an ORR of 43% and a median DoR of 11.1 months.
  • The World Health Organization announced that breast cancer is now the most common form of cancer worldwide. In 2020, 2.3 million new cases of breast cancer were diagnosed, accounting for 11.7% of all cancer cases. Lung cancer—which had been the most common malignancy for the past two decades—is now second, followed by colorectal cancer.

January 2021

January 22–28

  • The KRASG12C inhibitor sotorasib (Amgen) may be effective in patients with previously treated non–small cell lung cancer (NSCLC), according to results presented at the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer (WCLC), rescheduled from August and being held virtually January 28–31. In the phase II CodeBreak 100 trial, 124 patients had an objective response rate (ORR) of 37.1% and a median progression-free survival (PFS) of 6.8 months; responses lasted for a median of 10 months. Based on these data, Amgen filed for FDA approval of the drug in December 2020.
  • Also at the WCLC, researchers reported that amivantamab (Janssen) may be an effective therapy for patients with metastatic or inoperable NSCLC and EGFR exon 20 insertions who have already received chemotherapy. In the phase I CHRYSALIS trial, 40% of 81 patients responded; they had a median PFS of 8.3 months and a median overall survival (OS) of 22.8 months. Amivantamab is a bispecific antibody that targets EGFR and MET.
  • Datopotamab deruxtecan (AstraZeneca/Daiichi Sankyo) may be active in patients with advanced or metastatic NSCLC, researchers reported at the WCLC. In the phase I TROPION-PanTumor01 trial, 159 patients had ORRs ranging from 21% to 25%, depending on the dose; disease control rates ranged from 67% to 80%, and median PFS was 4.3 to 8.2 months. Datopotamab deruxtecan is an antibody–drug conjugate that consists of a TROP2-directed monoclonal antibody linked to a topoisomerase 1 inhibitor derived from exatecan.
  • Bristol Myers Squibb announced that the FDA approved nivolumab (Opdivo) plus cabozantinib (Cabometyx; Exelixis) for advanced renal cell carcinoma. The approval was based on the phase III CHECKMATE-9ER trial, in which newly diagnosed patients treated with the combination had a median PFS of 16.6 months and an overall response rate of 55.7%, compared with 8.3 months and 27.1%, respectively, in patients who received nivolumab, a PD-1 inhibitor, plus sunitinib (Sutent; Pfizer).
  • The American Lung Association released its 19th annual State of Tobacco Control report. The publication calls for ending sales of flavored tobacco products to reduce their use among kids as well as in Black communities. The report also highlights the increased need to prioritize smoking cessation during the COVID-19 pandemic, noting that smoking raises the risk of severe infection.
  • The National Comprehensive Cancer Network (NCCN) published guidelines on administering COVID-19 vaccines to patients with cancer. The document recommends vaccinating all patients undergoing active cancer treatment as soon as possible. It also offers suggestions for prioritizing patients for vaccines, scheduling inoculations around immunosuppressive therapy, and handling drug interactions or side effects, among other things.
  • U.S. cancer centers and organizations issued a public letter urging the resumption of cancer screening and treatment during the COVID-19 pandemic. The letter, which was written by the NCCN and the American Cancer Society, and signed by 76 other organizations, highlights considerable drops in cancer screening and diagnosis—as well as delays in treatment—during the pandemic.
  • President Joe Biden nominated Eric Lander, PhD, to serve as his science advisor and director of the Office of Science and Technology Policy, and Rochelle Walensky, MD, MPH, to lead the Centers for Disease Control and Prevention. Biden also appointed Janet Woodcock, MD, as acting commissioner of the FDA. Lander heads the Broad Institute of MIT and Harvard in Cambridge, MA, and Walensky is chief of the Infectious Diseases Division at Massachusetts General Hospital in Boston; Woodcock served as director of the FDA’s Center for Drug Evaluation and Research.

January 15–21

  • During the American Society of Clinical Oncology (ASCO) 2021 Gastrointestinal (GI) Cancers Symposium, held virtually January 15–17, researchers reported that adding bemarituzumab (FPA144; Five Prime) to chemotherapy may improve survival for patients with advanced gastric cancer and FGFR2b mutations. In the phase II FIGHT trial, patients treated with the combination had a median progression-free survival (PFS) of 9.5 months and did not reach median overall survival (OS), compared with 7.4 months and 12.9 months, respectively, in patients who received chemotherapy alone. Bemarituzumab is a targeted antibody that inhibits FBFR2b.
  • The investigational CD73 inhibitor AB680 (Arcus Biosciences) combined with nab-paclitaxel (Abraxane; Celgene) plus gemcitabine and zimberelimab (AB122; Arcus) may be effective in patients newly diagnosed with metastatic pancreatic cancer, researchers reported at the ASCO GI meeting. In a phase I trial, seven of 17 patients responded to the combination, and eight others experienced some tumor shrinkage.
  • The FDA approved fam-trastuzumab deruxtecan-nxki (Enhertu; Daiichi Sankyo) in patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who previously received trastuzumab (Herceptin; Genentech). The approval was based on the phase II DESTINY-Gastric01 trial, in which patients treated with the agent had a median OS of 12.5 months, compared with 8.4 months in patients who received chemotherapy. Fam-trastuzumab deruxtecan-nxki consists of the anti-HER2 monoclonal antibody trastuzumab connected to deruxtecan, a topoisomerase I inhibitor.
  • The Community Oncology Alliance requested that community oncologists be given priority approval to administer COVID-19 vaccinations to their patients with cancer and blood disorders who are immunocompromised. The request, which was made to state governors and the U.S. government, also asked that oncologists be provided with enough vaccines to complete the inoculations.
  • Black women in the United States may be at greater risk of breast cancer recurrence than white women, according to findings in JAMA Oncology. Researchers analyzed Oncotype DX Breast Recurrence Score tests from 86,033 women with breast cancer. They found that Black women were significantly more likely than white women to have a recurrence score greater than 25; moreover, Black women were more likely to die from breast cancer than white women with comparable recurrence risk. They also discovered that the prognostic accuracy of the recurrence score was significantly lower in Black women than white women, highlighting the need to calibrate such tests in more diverse populations.
  • GlaxoSmithKline reported that bintrafusp alfa (M7824) may not be effective at treating non–small cell lung cancer that expresses PD-L1. In the phase III INTR@PID Lung 037 trial, the drug did not improve PFS compared with the PD-1 inhibitor pembrolizumab (Keytruda; Merck), leading an independent data monitoring committee to recommend discontinuing the trial. A bifunctional immunotherapy that blocks TGFβ and PD-L1, bintrafusp alfa will continue testing in other trials.

January 8–14

  • Sanofi announced it will acquire Kymab for $1.1 billion up front and up to $350 million more in milestone payments. Sanofi will gain KY1044, an anti-ICOS antibody that is being tested alone and in combination with a PD-L1 inhibitor in solid cancers. Sanofi’s purchase also includes Kymab’s leading candidate KY1005, an anti-OX40L antibody being assessed for various immune disorders.
  • Novartis will pay BeiGene $650 million up front and as much as $1.55 billion in milestone payments for the PD-1 inhibitor tislelizumab. Novartis will acquire rights to develop, manufacture, and commercialize the drug in North America, Japan, the European Union, and six other European countries. Tislelizumab is approved in China for certain forms of classic Hodgkin lymphoma, urothelial carcinoma, and non–small cell lung cancer (NSCLC).
  • The American Cancer Society (ACS) reported that the cancer mortality rate decreased by 2.4% from 2017 to 2018 in the United States, the biggest single-year drop on record. The ACS estimated that there will be 1.9 million new cancer diagnoses and 600,000 cancer-related deaths in 2021. However, the projections don’t account for the COVID-19 pandemic, which has disrupted cancer screenings and care.
  • In The New England Journal of Medicine, a report revealed the distribution of KRASG12C mutations by race and sex. Researchers analyzed the prevalence of KRASG12C mutations in 32,138 patients with cancer, 13.8% of whom had NSCLC. They found that among patients with NSCLC, KRASG12C mutations occurred in 13% of white, 10.9% of Black, and 3.6% of Asian patients. This mutation was significantly more common in white and Asian women with NSCLC than their male counterparts.
  • The FDA approved crizotinib (Xalkori; Pfizer) in children and young adults with relapsed/refractory, systemic anaplastic large cell lymphoma who have ALK mutations. The approval was based on a phase I/II trial in which 26 patients had an objective response rate of 88% and a complete remission rate of 81%. An ALK inhibitor, crizotinib was previously approved for patients with NSCLC who have ALK or ROS1 mutations.
  • The FDA placed a clinical hold on Neoleukin Therapeutics’ phase I trial of NL-201. The agency asked Neoleukin to develop a new assay that more precisely measures dosing of the drug. NL-201 is a protein therapeutic that stimulates IL2 and IL15 signaling.
  • U.S. Customs and Border Protection and the FDA announced the seizure of counterfeit, unauthorized electronic cigarette (e-cigarette) cartridges. In January, a shipment of 33,681 cartridges was discovered at the Dallas Fort Worth International Airport in Texas. In December, the agencies seized 42 shipments of e-cigarette cartridges from China en route to several Texas counties. In both instances, the shipments included flavored cartridges that are illegal in the United States.

December 29–January 7

  • In The New England Journal of Medicine, a paper documented two instances of vaginal cancer transmission from mother to infant. Next-generation sequencing revealed that a 2-year-old and a 6-year-old boy with lung cancer developed the malignancies from uterine cervical tumors that were transferred from their mothers during childbirth. In each case, the child’s tumor lacked a Y chromosome, and shared somatic mutations, a human papillomavirus genome, and single-nucleotide polymorphism alleles with the mother’s tumor.
  • After consulting with the FDA, Bristol Myers Squibb withdrew nivolumab (Opdivo) from the U.S. market for patients with small cell lung cancer who had received prior therapies. The decision was based on the phase III CheckMate-451 and CheckMate-331 trials, in which the PD-1 inhibitor did not improve overall survival (OS) compared with standard therapies. The FDA had granted nivolumab an accelerated approval in August 2018 based on promising results in the phase I/II CheckMate-032 trial.
  • Adding bevacizumab (Avastin; Genentech) to osimertinib (Tagrisso; AstraZeneca) may not improve the latter’s efficacy in patients with EGFR-mutant non–small cell lung cancer (NSCLC), researchers reported in JAMA Oncology. In a phase II trial, the combination did not increase progression-free survival (PFS) or OS compared with osimertinib alone. Researchers had hypothesized that bevacizumab, an angiogenesis inhibitor, might amplify the effects of osimertinib, a tyrosine kinase inhibitor.
  • Calithera announced that its glutaminase inhibitor telaglenastat plus cabozantinib (Cabometyx; Exelixis) may not be effective in advanced or metastatic renal cell carcinoma. In the phase II CANTATA trial, the combination did not improve PFS compared with cabozantinib alone. Given the negative results, the company will cut its workforce by approximately 35%, although testing will continue in NSCLC.
  • Eprenetapopt (APR-246; Aprea Therapeutics) plus azacitidine failed to improve outcomes in patients with TP53-mutant myelodysplastic syndromes. In a phase III trial, the combination did not significantly increase the complete remission rate compared with azacitidine alone, although the company will continue to analyze the data as it matures. Eprenetapopt is a small molecule that reactivates mutant TP53.
  • Men of African ancestry may be at higher risk of developing prostate cancer than those of European ancestry, according to findings in Nature Genetics. Researchers conducted a meta-analysis of prostate cancer studies that included 107,247 patients and 127,006 control subjects. They identified 86 new genetic risk variants associated with the disease and determined that men of African descent had a risk score that was 2.18 times higher on average than that of men with European backgrounds.

Back to top

Cancer Discovery Editorial Office
American Association for Cancer Research  |  Publishing Division
615 Chestnut Street  |  17th Floor  |  Philadelphia, PA 19106-4404
Phone: (215) 440-9300  |  Fax: (215) 446-7297  |  E-mail:  cancerdiscovery@aacr.org