The FDA expanded the approval of pembrolizumab to include the treatment of women with recurrent or metastatic cervical cancer who have PD-L1-expressing tumors that progressed on or after chemotherapy.
Researchers defined PD-L1 expression as combined positive score (CPS) of at least 1 as determined by an FDA-approved test.
Pembrolizumab (Keytruda, Merck) — an anti-PD-1 therapy — is indicated for the treatment of certain patients with melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, Hodgkin lymphoma, urothelial carcinoma and gastric cancer.
In March, FDA granted pembrolizumab priority review for the treatment of women with advanced cervical cancer whose disease progressed on or after chemotherapy.
“Keytruda is now the first anti-PD-1 therapy approved for the treatment of advanced cervical cancer, providing an important new second-line option for certain patients with this disease,” Roy Baynes, MD, PhD, senior vice president, head of global clinical development and chief medical officer at Merck, said in a company-issued press release. “This approval also marks the first indication for Keytruda in a gynecologic cancer and reflects our ongoing commitment to bring forward innovative treatment options across a broad range of cancers, including cancers that disproportionately affect women.”
FDA based the expanded approval on results from the KEYNOTE-158 trial, which assessed 98 patients with recurrent or metastatic cervical cancer. Seventy-nine percent of patients had PD-L1 expression (CPS 1) and had received at least one line of chemotherapy in the metastatic setting.
Among those patients, researchers observed an objective response rate of 14.3% (95% CI, 7.4-24.1), with a complete response rate of 2.6% and partial response rate of 11.7%.
Median duration of response had not been reached (range, 4.1 to 18.6+ months) among the 11 responding patients. Ninety-one percent of patients experienced responses that lasted 6 months or longer. Researchers did not observe responses among patients whose tumors did not express PD-L1 (CPS < 1).
The most common adverse reactions among patients with cervical cancer included fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).
Eight percent of patients discontinued pembrolizumab due to adverse reactions.
Serious adverse reactions occurred among 39% of patients. The most frequent serious adverse reactions reported included anemia (7%), fistula (4.1%), hemorrhage (4.1%) and infections (4.1%).
“Even with the many advances observed across gynecologic cancers, new treatment options have been lacking for previously treated patients with advanced cervical cancer,” Bradley Monk, MD, FACOG, FACS, oncologist with Arizona Oncology, medical director of US Oncology Research’s gynecology program, and professor of obstetrics and gynecology at University of Arizona’s College of Medicine and Creighton University School of Medicine, said in the press release. “The approval of Keytruda in this indication is important news — and, as an oncologist, it is exciting to see a much-needed option made available to these patients.”