Cervical cancer cases are on the decline in the U.S. thanks to increased screening and vaccination with Merck & Co.’s Gardasil. Now, the New Jersey pharma has shown that for patients who unfortunately get cervical cancer, its immunotherapy Keytruda could save lives.
Among patients with persistent, recurrent or metastatic cervical cancer who weren’t previously treated with systemic therapy, adding Keytruda to chemotherapy with or without Roche’s Avastin reduced the risk of death by 33% in a phase 3 trial, Merck said at the European Society for Medical Oncology 2021 virtual congress.
The win, from the KEYNOTE-826 trial, marks the first time a PD-1 inhibitor showed a survival benefit in front-line cervical cancer. It covers patients regardless of whether their tumors expressed PD-L1, a biomarker that’s often linked to better response to PD-1/L1 agents.
Patients who got Keytruda lived a median 24.4 months compared with 16.5 months for those who received standard chemotherapy with or without Avastin. At the two-year mark, 50.4% of Keytruda takers were alive, versus 40.4% of control patients.
“This is a practice-changing study,” Antonio González-Martín, M.D., cancer center director of Clínica Universidad de Navarra, said in a statement. “The data are so solid in terms of increment in overall survival that this combination should be considered the new standard of care for women with persistent, recurrent or metastatic cervical cancer.”
Previously, Avastin has showed it could prolong survival on top of chemotherapy by 3.7 months, study investigator Nicoletta Colombo, M.D., of the European Institute of Oncology noted in a statement. For KEYNOTE-826, Avastin was included at a physician's discretion. Its use was balanced in the two arms at a little above 60% of patients, meaning it didn’t skew the final results, Vicki Goodman, vice president of clinical research at Merck Research Laboratories, said in an interview.
Keytruda helped patients regardless of whether they took Avastin, but those on the anti-VEGF drug enjoyed better treatment outcomes. Among patients who also received Avastin, the addition of Keytruda slashed the risk of death by 37%. Among those who received Keytruda and chemotherapy without Avastin, the reduction magnitude fell to 26% over chemo alone. Goodman cautioned that the study wasn’t designed to statistically review this subgroup analysis. Some patients have underlying disease or other medical history that made them inappropriate for Avastin, she added.
Thanks to an FDA accelerated approval, Keytruda is currently used as a monotherapy in post-chemo second-line treatment of metastatic cervical cancer that express PD-L1. A phase 3 trial dubbed KEYNOTE-A18 is testing chemoradiotherapy with or without Keytruda for locally advanced cervical cancer.
“One of the important points of bringing Keytruda forward into earlier lines of therapy is moving it into a potentially curative setting, where the immune system is relatively intact relative to metastatic disease,” Goodman said.
Merck isn’t alone in the pursuit of moving immunotherapy into earlier cervical cancer treatment. AstraZeneca, in the phase 3 CALLA trial, is testing its PD-L1 inhibitor Imfinzi alongside concurrent chemoradiation therapy in locally advanced cervical cancer.