Behind KEYNOTE-826 in Persistent, Recurrent, or Metastatic Cervical Cancer

Bradley J. Monk, MD, FACS, FACOG, professor, division of gynecologic oncology, University of Arizona College of Medicine, Creighton University School of Medicine, director, principal investigator, community research development, HonorHealth Research Institute, vice president and member board of directors GOG-Foundation, co-director GOG-partners, discusses the rationale behind the KEYNOTE-826 study (NCT03635567).

In the phase 3, double-blind, placebo-controlled KEYNOTE-826 trial, the efficacy and safety of pembrolizumab (Keytruda) plus platinum-based chemotherapy with or without bevacizumab (Avastin) is being evaluated as a treatment for patients with persistent, recurrent, or metastatic cervical cancer.

Primary end points of the study are progression-free survival (PFS) and overall survival, and secondary end points include objective response rate, duration of response, PFS at month 12, PFS per RECIST v1.1, the number of patients with adverse events (AEs), the number of patients with serious AEs, the percentage of patients who experience immune-related AEs, the number of treatment discontinuations in the study, and the number of patients with a 10-point change from baseline in quality of life.

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0:10 | Virtually all cervical cancers are caused by the human papilloma virus, what we call HPV. We developed a vaccine in 2006, which is almost 100% effective in preventing this infection, and we can test for the virus on the cervix and determine a woman's risk. But that's not happening. And because that's not happening, cervical cancer is the fourth most common cause of cancer related deaths worldwide. There are more than 4000 deaths in the [United States] every year, and there has been a plateau for more than 20 years.

0:46 | I have to say that because this is a preventable cancer. Because we are not achieving our goals, we need to find better treatments for women whose cervical cancer is life threatening. Those are really 3 categories. Those are categories who get chemotherapy and radiation, and it doesn't go away. It's also women whose cancers come back, recurrent, and then thirdly, it's women who have de novo widely metastatic disease stage IV.

1:16 | Because this is a virally induced cancer, it should be susceptible to immunotherapy, immunotherapy with an immune checkpoint inhibitor, immunotherapy with pembrolizumab, which is a humanized monoclonal antibody against PD-L1. In fact, we had preliminary data only on 77 patients with a response rate of only 14.3%, which led to the FDA approval in June of 2018. Now, although responses were rare, they were durable, and it was tolerable. We committed to do a confirmatory trial, and that accelerated approval was in the second-line. We committed to a randomized phase 3 trial in the first-line, persistent recurrent stage IV setting, adding it to available therapy to see if we can help women live longer and live better. That study is called KEYNOTE-826. Based on a preliminary result with follow-up of less than 2 years, it got FDA approval on October 13, 2021, so [it was an] accelerated approval.