Noted This Week

November 13–19

Merck’s pembrolizumab (Keytruda) in combination with chemotherapy was approved to treat metastatic triple-negative breast cancer (TNBC) in patients with a PD-L1 combined positive score of at least 10. The FDA also approved the PD-L1 IHC 22C3 pharmDx (Dako North American) as a companion diagnostic to determine eligibility for pembrolizumab. In the KEYNOTE-355 trial, patients with TNBC who received the drug combination had a median progression-free survival of 9.7 months, compared with 5.6 months in patients who received chemotherapy alone.

The 194 member countries of the World Health Organization (WHO) set a strategy to speed the elimination of cervical cancer. The plan calls for all nations to vaccinate 90% of girls by age 15 against human papillomavirus; screen at least 70% of women once by age 35 and again by age 45 with a high-performance test; and ensure that at least 90% of women receive treatment for precancer and invasive disease. Reaching these targets by 2030 would drive down the incidence of cervical cancer by 10% by decade’s end, “setting the world on the path to avert 70 million cases in the century,” according to the WHO.

In a retrospective study published in Cancer Cell, researchers identified molecular features in 26 of 111 patients (23.4%) with various cancers that could explain exceptional responses to treatment, such as the co-occurrence of multiple rare genetic changes in the tumor genome or the infiltration of the tumor with certain types of immune cells. The work, part of the NCI’s Exceptional Responders Initiative, which launched in 2014, involved analyzing tumor tissue with multiple genomic approaches, including analysis of DNA mutations, RNA expression levels, DNA copy-number alterations, and DNA methylation. Exceptional responders were those who responded to a treatment effective in less than 10% of similar patients; exceptional responses were defined as lasting at least three times as long as the median response time.

At its annual meeting, the Friends of Cancer Research issued a white paper suggesting possible improvements to the FDA’s Accelerated Approval Program, which allows for earlier approval of drugs that treat serious and life-threatening illnesses based on a surrogate or intermediate clinical endpoint that is reasonably likely to predict a clinical benefit. For example, the white paper notes that it might be appropriate to grant an accelerated approval to a drug with a lower overall response rate "if the drug is less toxic or has a positive impact on patient-reported outcomes of function." Although the FDA looks at a risk–benefit assessment, the agency is legally bound to focus on surrogate and intermediate clinical endpoints when making these approval decisions.

The American Association for Cancer Research and the FDA have launched Project Livin' Label, an educational initiative to foster broad understanding of specific cancer drugs. For each featured product, the FDA’s Oncology Center of Excellence will moderate a panel discussion with an FDA reviewer, an academic clinical trial investigator, a patient, and a representative from the company that developed the drug about its backstory and safe and effective use. The sessions will be available on demand; the first episode will focus on tucatinib (Tukysa; Seagen), a second-line treatment for metastatic HER2+ breast cancer.


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