Noted This Week
Cancer-related news briefs by week
April 14–20, 2017
- Genentech’s PD-L1 inhibitor atezolizumab (Tecentriq) received the FDA’s nod as first-line therapy for patients with locally advanced or metastatic urothelial carcinoma who aren’t eligible for platinum chemotherapy. This is the first immune checkpoint blocker to gain approval as initial treatment for bladder cancer. The FDA based its decision on data from a phase II study in which the objective response rate to atezolizumab among 119 patients was 23.5%, including a complete response rate of 6.7%.
- AbbVie announced disappointing results from two phase III studies evaluating veliparib, an investigational PARP inhibitor, in combination with carboplatin and paclitaxel, in non–small cell lung cancer (NSCLC) and triple-negative breast cancer (TNBC). Neither trial met its primary endpoint—overall survival for NSCLC; pathologic complete response (pCR) for TNBC.
- The FDA designated CTL019 as a Breakthrough Therapy for diffuse large B-cell lymphoma (DLBCL). Results of a phase II study supporting the designation will be presented at an upcoming meeting, according to Novartis. Business news outlet TheStreet reported that investors are keen to compare the data on this investigational chimeric antigen receptor (CAR) T-cell therapy to that of KTE-C19 (Kite Pharma), another CD19-targeting CAR T-cell therapy under review as a treatment for DLBCL.
- TheStreet also noted that the FDA’s decision to spend only 5 hours reviewing neratinib for breast cancer may be a bad omen for Puma Biotechnology. In recent years, the agency “has often used half-day sessions of the Oncologic Drugs Advisory Committee to administer public floggings to flawed cancer drugs”—for instance, Spectrum’s apaziquone for bladder cancer last September. The phase III study data for neratinib, a pan-HER inhibitor, indicate only a modest improvement in disease-free survival at the cost of high rates of severe diarrhea.
- A study in JAMA Surgery suggests that patients with early-stage breast cancer who have a pCR to neoadjuvant chemotherapy may be able to avoid surgery. In an analysis of 527 patients, those who achieved a pCR were also more than seven times less likely to have residual nodal disease. The investigators plan to test whether radiation would be just as effective as surgery for this subset in an upcoming phase II trial.
- As part of the 21st Century Cures Act, the University of Kentucky (UK) in Lexington was awarded $11.2 million from the NIH to study cancer and obesity. The 5-year grant will help fund UK’s new Center for Cancer and Metabolism. University leaders hailed the funding announcement, noting that Kentucky has one of the nation’s highest cancer mortality rates and is also in the top 10 for obesity, so research into these major health issues is sorely needed.
April 7–13, 2017
- The U.S. Preventive Services Task Force issued a draft recommendation in support of an individualized approach to prostate cancer screening, with a decision based upon a discussion with a health-care provider about the risks and potential benefits of screening, for men ages 55 to 69. In 2012, the group recommended against routine screening for all men, even though the American Urological Association and other organizations supported it for men who discussed the pros and cons with a clinician. The public can comment on the draft recommendation until May 8.
- According to a report by the International Agency for Research on Cancer (IARC), published in Lancet Oncology, the number of childhood cancers worldwide rose by 13% between the 1980s and the period spanning 2001 to 2010. That conclusion was based upon numbers recorded in 153 cancer registries in 62 countries, mainly in North American and Europe. IARC attributes part of the increase to improved detection efforts.
- GenomeWeb reported that the University of California (UC) filed an appeal related to a patent dispute with the Broad Institute over CRISPR/Cas9 technology with the U.S. Court of Appeals for the Federal Circuit. In February, the Patent Trials and Appeals Board sided with the Broad Institute, saying that the institute’s patents specified use in eukaryotic cells and thus didn’t overlap with patent applications from the university. However, the UC claims that its researchers were the first to engineer CRISPR/Cas9 for use in all environments.
- The FDA granted Orphan Drug Designation to two experimental therapies: ganitumab (NantCell) and tasquinimod (Active Biotech). A monoclonal antibody directed against IGF1R, ganitumab is being tested in a phase III trial for the treatment of Ewing sarcoma. Tasquinimod is an immunomodulatory, antimetastatic, and antiangiogenic compound under investigation for the treatment of multiple myeloma.
- Research from a team of scientists at École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, and a second group from EPFL and Katholieke Universiteit Leuven in Belgium, published back to back in Science Translational Medicine, shows that the combined use of angiogenesis inhibitors and PD-1 checkpoint blockers shrank tumors and improved survival in mice with different types of cancer, including breast and pancreatic malignancies. Anti–PD-1 drugs work in only about 20% to 40% of patients with certain types of cancer, such as melanoma, so researchers have been testing therapeutic combinations in an effort enhance cytotoxic T-cell activity.
- Although it was shown to improve survival in patients with certain head and neck cancers in a phase III trial, the PD-1 inhibitor nivolumab (Opdivo) will not be recommended to treat these patients in the UK. The decision was based on a cost/benefit analysis by the National Institute for Health and Care Excellence (NICE), prompting calls from clinicians and the public for NICE to work with the drug’s maker, Bristol-Myers Squibb, to agree on an acceptable price.
April 1–6, 2017
This Week: Special Content from the American Association for Cancer Research’s (AACR) Annual Meeting 2017 and other news
- In a position statement, the American Society of Clinical Oncology raised serious concerns about recently proposed federal “right-to-try” (RTT) legislation, as well as RTT state laws that have been enacted. Although the organization supports increasing access to investigational treatments for patients with cancer, it asserted that most RTT laws are “not an effective mechanism for improving access to investigational drugs for terminally ill patients and may cause unintended harms.” The statement notes that RTT laws do not require or compel drug manufacturers to provide investigational products or offer new rights or protections for patients.
- Roche announced that alectinib (Alecensa) significantly improved progression-free survival in people with ALK-positive advanced non–small cell lung cancer whose disease had progressed following treatment with a platinum-based chemotherapy and crizotinib (Xalkori; Pfizer). The company said that peer-reviewed data from this phase III study will be published later this year.
- The Roche CINtec Histology test received marketing clearance from the FDA. The test is the only clinically validated p16 biomarker test that, when used in conjunction with hematoxylin and eosin staining, helps pathologists determine which women should receive treatment for precancerous cervical lesions.
- Reflecting on much of the research presented at the American Association for Cancer Research (AACR) Annual Meeting in Washington, DC, Louis Weiner, MD, director of the Georgetown Lombardi Cancer Center in Washington, DC, and moderator of an April 4 press conference on immunotherapeutics, said that long-held dogma has changed. “It wasn’t so long ago, maybe even only a decade ago, that people thought that immunotherapy was kind of like a stupid pet trick when it came to the treatment of cancer,” he noted. “That certainly has been disproven.”
- During a plenary address at the AACR meeting, Jennifer Grandis, MD, of the Helen Diller Comprehensive Cancer Center at the University of California, San Francisco, outlined the benefits of “window-of-opportunity” trials, in which patients are treated with a novel drug that has exhibited strong preclinical activity prior to tumor resection. Researchers can then use tumor samples to gain insight into the pharmacodynamics of the drug, resistance mechanisms, and biomarkers of response. These trials, she said, “expand the scope of clinical research programs” and can speed improvements in cancer treatment.
- During a science policy session, researchers from the United States and the UK presented differing views of electronic cigarettes, or e-cigarettes, as a smoking cessation tool. Ben Toll, PhD, of the Medical University of South Carolina in Charleston, noted that American guidelines call for oncologists to recommend only FDA-approved cessation tools, such as nicotine patches and gum, because they have proven effective. However, Lion Shahab, PhD, of University College London said that British doctors aren’t quite as leery of the devices because there’s little evidence that they’ll cause harm while potentially conveying a small benefit to users.
- Several organizations have begun to collaborate on the Human Cancer Model Initiative, which was described by Mathew Garnett, PhD, of the UK’s Wellcome Trust Sanger Institute, during a Stand Up To Cancer scientific session. The participating institutions—Cancer Research UK, Hubrecht Organoid Technology, the NCI, the Wellcome Trust Sanger Institute, Cold Spring Harbor Laboratory in New York, and the Broad Institute in Cambridge, MA—aim to generate 1,000 highly annotated tumor-derived models and make them available to researchers through the American Type Culture Collection.
- On Monday, April 3, former Vice President Joe Biden gave an inspirational and at times moving speech about the Beau Biden Cancer Moonshot, named for his son, rattling off several of the collaborative projects that the Moonshot has launched, including the engagement of dozens of federal agencies with a stake in cancer research, dedication to greater sharing of deidentified patient records, efforts to boost enrollment in clinical trials, and a push to standardize electronic medical records. However, the work has only just begun. “I’d like to tell you we solved all of the problems we identified and that you know so well,” Biden said. “In the time we’ve had, we got a running start, but we’re nowhere near finishing the race.”
- Biden also sought to reassure attendees at the AACR meeting that congressional support for the NIH remains high, even though President Donald Trump proposed what Biden called “draconian cuts” of nearly 20% to the agency’s budget for the 2018 fiscal year. “Here’s the good news—I don’t think that there’s a chance that the American people or the United States Congress, virtually the same Congress that passed the 21st Century Cures Act just several months ago, will support or pass this budget.”
- During a panel discussion that followed Biden’s speech, Representative Kevin Yoder of Kansas, a Republican, echoed Biden’s sentiments. “Regardless of who is in the White House, this continues to be a priority for us,” Yoder said. “This isn’t just a line item in the budget … but something that really is fundamental to who we are as American people.” He continued by saying that cancer doesn’t affect just one political party or one region of the country: “It knows no particular region. It affects every street, every cul-de-sac in America and therefore it affects every member of Congress and their constituents.”
- The future of immuno-oncology may involve “using anticancer probiotics to normalize an individual’s cancer–immune set point [inherent immunologic status],” said Laurence Zitvogel, MD, of Institut Gustave Roussy in France, during the April 3 plenary session. She noted that in a study of 175 patients given anti–PD-1 therapy, outcomes were poorer among those who also received antibiotics, which induced dysbiosis, or an imbalance in gut flora, determined through quantitative metagenomic analyses of patients’ stool composition. However, in mice bearing human non–small cell lung cancer, fecal microbiota transplantation restored the efficacy of PD-1 blockade; in particular, two microbial species, Akkermansia muciniphila and Enterococcus hirae, had important immunomodulatory effects.
- Reviewing the field of chimeric antigen receptor (CAR) T-cell therapy during the same plenary session, Crystal Mackall, MD, of Stanford University in California, described antigen loss—a ready route for tumor cells to evade engineered T cells that target single tumor antigens—as a “canary in the coal mine” in forewarning resistance/relapse. Better CARs are on the horizon, she said, including a bispecific iteration that simultaneously goes after CD19 and CD22, both highly expressed in B-cell malignancies. “You will witness, in the near future, the delivery of increasingly complex, intelligent cellular therapeutics”—for instance, remote-controlled, exhaustion-resistant CAR T cells to diminish toxicity and improve efficacy—“to help ensure that genetically quiet cancers can still benefit from the immunotherapy revolution,” she concluded.
- Attendees of the April 2 Opening Ceremony at the AACR’s meeting stood together to call upon Congress to maintain—if not increase—NIH funding. After hearing an impassioned plea from AACR President Nancy Davidson, MD, that scientific funding must remain a national priority, the audience of thousands raised and waved signs bearing slogans such as “Cancer Research Saves Lives,” “Support Medical Research,” and “Invest in Life-Saving Cancer Research.”
- For patients lacking tumor tissue, a liquid biopsy can detect the emergence of new mutations, such as the EGFR T790M mutation in patients with non–small cell lung cancer. However, due to a variety of concerns, such as reproducibility and variation among assays, testing tissue samples remains the gold standard, said Phil Stephens, PhD, of Foundation Medicine in Cambridge, MA, during a panel discussion on liquid biopsies. Yet even if tissue is available, argued Howard Scher, MD, of Memorial Sloan Kettering Cancer Center in New York, NY, liquid biopsies may make more sense in some cases, such as in metastatic prostate cancer, where extracting tissue from bone can be painful and difficult for patients.
- Following up on interim results reported last spring, Italian researchers presented final data on patients with HER2-positive metastatic colorectal cancer enrolled in Cohort A of the phase II HERACLES trial, which tested the combination of trastuzumab (Herceptin; Genentech) and lapatinib (Tykerb; GlaxoSmithKline). The objective response rate (ORR) was 30% (10 of 33 patients), including two complete responses; thirteen patients had stable disease. The ORR was even higher—50%—in patients with tumors with highly amplified HER2.
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