Noted This Week
This Week: Special Content from the American Association for Cancer Research’s (AACR) Annual Meeting 2018 and other news
Speaking at the AACR meeting’s Opening Plenary, Padmanee Sharma, MD, PhD, offered a brief history of the development of checkpoint inhibitors and efforts to discover and study additional targets, such as CD40 and ICOS for costimulation of T cells, and CD47 and VISTA, which are predominantly expressed on macrophages. "Immune checkpoint therapies are certainly joining the ranks of surgery, radiation, and chemotherapy as a pillar of cancer research," she said. "We need to understand that multiple immune checkpoints exist and are dynamic in their expression."
George Coukos, MD, PhD, of the Ludwig Center for Cancer Research, University of Lausanne, Switzerland, presented data from a pilot clinical trial that tested personalized neoantigen vaccines in 25 patients with recurrent ovarian cancer. Data showed that the therapy was feasible, well tolerated, and safe, both alone and in combination with one or the two other treatments. Patients in whom the vaccine could effectively mobilize neoepitope-specific T-cell responses had significantly prolonged survival.
"I would say that it's like Coke and Pepsi—they’re two similar flavors from two different companies in two different packages," said Antoni Ribas, MD, PhD, of the University of California, Los Angeles, in comparing the PD-1 inhibitors nivolumab (Opdivo; Bristol-Myers Squibb) and pembrolizumab (Keytruda; Merck).
The Lustgarten Foundation and Stand Up To Cancer (SU2C) announced that they are partnering to accelerate research to increase survival of patients with pancreatic cancer. The two groups will fund the Pancreatic Cancer Collective with an initial commitment of $25 million. The money will be used to launch new collaborative efforts, leverage artificial intelligence, improve and develop new diagnostics and treatments for pancreatic cancer, and support the next generation of pancreatic cancer researchers. The AACR is SU2C’s scientific partner.
The AACR and the UBS Oncology Impact Fund (OIF) managed by MPM Capital announced a gift of $1.25 million to fund the joint AACR–MPM Transformative Cancer Research Grants Program to support innovative research that will accelerate breakthroughs in the treatment of cancer. The OIF is a first-of-its-kind social-impact fund dedicated to investing in oncology therapeutics across a spectrum of companies, from early-stage start-ups to public companies. The AACR and MPM are now establishing an expert scientific advisory board whose members will be tasked with selecting grant recipients.
Children with non-chromosomal birth defects are 2.5 times more likely to develop childhood cancers, according to findings presented by Jeremy Schraw, PhD, of Baylor College of Medicine in Houston, TX. Reviewing data on 10.1 million births, Schraw and his team found even stronger associations between certain birth defects and specific cancers—for example, children with spina bifida without anencephaly were at a 74.9-fold higher risk of developing non-rhabdomyosarcoma soft-tissue sarcoma. "We need to better understand the ages at which those children are at risk, we need to validate the findings, and we need to understand the mechanism of that association better before we start making decisions about screening and treatment," he said.
Updated MOSCATO-01 trial results indicate tailoring treatment to the genetic makeup of a patient’s tumor may not improve overall survival (OS). Researchers reported that patients who were matched to targeted therapies based on “actionable” genetic mutations did not have significantly better OS than those who were not. Previous findings from the MOSCATO-1 trial indicated that 33% of patients matched to therapies based on genetic alterations experienced an extended progression-free survival of 30%.
Nivolumab offers a long-term survival benefit to patients with recurrent or metastatic squamous cell carcinoma of the head and neck, according to results of the phase III CheckMate 141 clinical trial presented at the meeting by Robert Ferris, MD, PhD, of the University of Pittsburgh, PA. After 2 years of follow-up, patients who received nivolumab had an OS rate of 16.9%, compared with 6% in patients treated with the investigator’s choice of drug. In patients with PD-L1 tumor expression above and below 1%, the risk of death was reduced by 45% and 27%, respectively. The findings confirm results reported after 1 year of follow-up.
Daniel J. Lenihan, MD, of the Washington University School of Medicine in St. Louis, MO, emphasized the need to consider cardiac issues beyond heart failure in patients receiving cancer treatment. "If you're looking for problems just related to heart failure, you're missing half the boat," he explained, noting that, in the PROTECT study, heart failure represented 50% of the adverse cardiac events experienced by patients with multiple myeloma receiving the proteasome inhibitor carfilzomib (Kyprolis; Onyx). "I really think our new definition of cardiotoxicities must include a lot more," he said, including metabolic issues and structural problems.
"There’s a tremendous effort to enroll minorities in clinical trials with the idea that the drugs work differently in minorities," said Otis Brawley, MD, chief medical and scientific officer and executive vice president of the American Cancer Society, who spoke about disparities in cancer treatment and mortality. "What’s frustrating to me is the data show minorities … aren’t [subsequently] getting the drugs."
Leaders of the AACR and Cancer Research UK announced the launch of an international alliance to speed progress against cancer. The alliance will build trans-Atlantic collaborations by establishing training and exchange programs, catalyzing scientific innovation by convening meetings and workshops, and uniting the cancer community to influence global research policy. The partnership will also foster links between laboratories and clinics in the United States and the UK.
In other news, the FDA approved osimertinib (Tagrisso) for first-line treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have EGFR mutations, AstraZeneca announced. The approval is based on results of the phase III FLAURA trial. The drug was previously approved for use in patients with EGFR-mutant NSCLC whose disease progressed on or after taking another EGFR therapy and who have developed the secondary T790M mutation. The FDA expanded the use of Roche’s Cobas EGFR Mutation Test v2 to detect the mutations.