Noted This Week

June 8–14

During the past week the FDA approved a host of drugs and approved expanded use of a companion diagnostic. Among the announcements:

  • Merck’s PD-1 checkpoint inhibitor pembrolizumab (Keytruda) was greenlighted for the treatment of advanced cervical cancer in women whose disease has progressed on or after chemotherapy and whose tumors express PD-L1. The approval was based on findings of a study in which 77 patients with PD-L1 levels of at least 1% had an overall response rate (ORR) of 14.3%; of those women, nearly all responded to the drug for at least 6 months.
  • In conjunction with that pembrolizumab approval, the agency OK’d the expanded use of Agilent’s PD-L1 IHC 223C pharmDx Kit to determine PD-L1 status.
  • Pembrolizumab was also approved for the treatment of primary mediastinal large B-cell lymphoma in adults and children, as well as those who have relapsed following at least two other treatments. The decision was based on a phase III trial in which patients treated with the immunotherapeutic had an ORR of 45%.
  • Genentech’s bevacizumab (Avastin) plus chemotherapy, followed by bevacizumab monotherapy, was approved for women with advanced ovarian cancer after surgery. In a phase III trial, patients who received that regimen had a median progression-free survival (PFS) of 18.2 months and a median overall survival (OS) of 43.8 months, compared with a PFS of 12.8 months and an OS of 40.6 months in patients who received the combination followed by a placebo.
  • The agency also expanded the indication for venetoclax (Venclexta; AbbVie and Genentech). It can now be used with rituximab for second-line treatment of patients with chronic lymphocytic leukemia or small lymphocytic lymphoma with or without a 17p deletion. Patients who received this combination regimen as part of a phase III trial had an ORR of 92% and did not reach median PFS, compared with an ORR of 72% and a PFS of 18.1 months in patients who received bendamustine plus rituximab.

The U.S. House of Representatives’ Subcommittee on Labor, Health and Human Services, and Education marked up its appropriations bill for the 2019 fiscal year. The bill proposes $38.3 billion in funding for the NIH, an increase of $1.25 billion. In addition, it proposes a total of $6.136 billion for the NCI, which includes $400 million authorized for the Beau Biden Cancer Moonshot. The bill now goes to the full House Appropriations Committee for consideration; the U.S. Senate has yet to mark up its spending bill.

Gene editing with CRISPR/Cas9 may increase cancer risk, according to two studies in Nature Medicine. The studies, which focused on retinal cells and pluripotent stem cells, found that CRISPR/Cas9 is most effective in human cells that lack functioning p53, a protein that responds to DNA damage by repairing it or instructing cells to self-destruct . However, cells with p53 mutations, although more likely to survive CRISPR/Cas9 editing, are also more likely to cause cancer.

In a Nature Genetics study, researchers reported the identification of 63 new prostate cancer susceptibility loci. The team then used the loci, along with loci from previous studies, to develop a new polygenic risk score. They determined that men who score in the top 1% are 5.7 times more likely to develop prostate cancer than the general population.


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