FDA approves Keytruda regimen as first-line treatment for cervical cancer
The FDA approved a combination of pembrolizumab and chemotherapy, with or without bevacizumab, for certain women with persistent, recurrent or metastatic cervical cancer.
The approval applies to women with tumors that express PD-L1 with a combined positive score (CPS) of 1 or greater, as indicated by an FDA-approved test.
The agency also converted from accelerated to regular approval use of pembrolizumab alone for this subgroup of women with disease progression on or after chemotherapy. The accelerated approval had been granted in June 2018 with the companion diagnostic PD-L1 IHC 22C3pharmDx (Dako North America Inc.), according to an FDA press release.
“Cervical cancer more commonly affects younger women and certain women of color in the U.S., and unfortunately, women diagnosed with persistent, recurrent or metastatic cervical cancer often have a low survival rate,” Bradley Monk, MD, FACOG, FACS, oncologist with Arizona Oncology, medical director of U.S. Oncology Research Gynecology Program and professor of obstetrics and gynecology at University of Arizona’s College of Medicine and Creighton University School of Medicine, said in a Merck-issued press release. “There have been no first-line approvals for women with persistent, recurrent or metastatic cervical cancer in the past 7 years. I am excited for today’s approval of a new combination with Keytruda, which offers a new treatment option for appropriate patients.”
The FDA based approval of the combination on results of the randomized phase 3 KEYNOTE-826 trial, presented last month during the virtual ESMO Congress 2021. The trial included 617 women with persistent, recurrent or metastatic cervical cancer who had not been treated with systemic chemotherapy.
Researchers randomly assigned the women 1:1 to 200 mg pembrolizumab (Keytruda, Merck) or placebo every 3 weeks for up to 35 cycles. All women also received chemotherapy with paclitaxel and cisplatin or carboplatin, and 63.6% in the pembrolizumab group and 62.5% in the placebo group also received bevacizumab (Avastin, Genentech).
Investigator-assessed OS and PFS served as main efficacy outcome measures.
Treatment continued for 2 years or until disease progression or unacceptable toxicity.
Among 548 women with a tumor PD-L1 CPS of 1 or greater, median OS was not reached (95% CI; 19.8 to not reached) in the pembrolizumab group and 16.3 months (95% CI, 14.5-19.4) in the placebo group (HR = 0.64; 95% CI, 0.5-0.81). Results previously reported by Healio also showed median PFS of 10.4 months with pembrolizumab vs. 8.2 months with placebo (HR = 0.62; 95% CI, 0.5-0.77). The pembrolizumab group also had a higher objective response rate (68% vs. 50%) and longer median duration of response (18 months vs. 10.4 months).
The most frequently reported adverse events among women who received pembrolizumab, chemotherapy and bevacizumab included peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism and decreased appetite.