Today’s approval was based on the Phase III KEYNOTE-826 trial that evaluated Keytruda and chemotherapy with or without bevacizumab compared to the same chemotherapy treatment.
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Merck’s bestselling, blockbuster checkpoint inhibitor Keytruda (pembrolizumab) picked up yet another indication, this time with chemotherapy, with or without bevacizumab, for persistent, recurrent or metastatic cervical cancer. These tumors express PD-L1 as determined by an assay approved by the U.S. Food and Drug Administration (FDA).
Keytruda is one of the most tested, if not the most tested, drugs in the industry, with more than 1,600 clinical trials ongoing currently. The company had six specific announcements related to the drug since the beginning of September, not including the FDA’s approval on August 31 for the drug for first-line advanced urothelial (bladder) carcinoma. That announcement was a conversion from an accelerated to a full (regular) approval.
Others include its approval in China in combination with chemotherapy for first-line locally advanced unresectable or metastatic esophageal or gastroesophageal junction (GEJ) carcinoma; a positive recommendation in Europe for Keytruda with chemotherapy in locally recurrent unresectable or metastatic triple-negative breast cancer; full results from the Phase III KEYNOTE-826 trial of the drug with chemotherapy with or without bevacizumab for first-line treatment of persistent, recurrent or metastatic cervical cancer; first results from the Phase III KEYNOTE-716 trial, where the drug as adjuvant treatment demonstrated statistically significant and clinically meaningful improvement in recurrence-free survival in resected high-risk stage II melanoma; and more.
Today’s approval was based on the Phase III KEYNOTE-826 trial that evaluated Keytruda and chemotherapy (paclitaxel plus cisplatin or paclitaxel plus carboplatin) with or without bevacizumab compared to the same chemotherapy treatment, with or without bevacizumab. The treatment with Keytruda demonstrated superior overall survival (OS) and progression-free survival (PFS) in patients whose tumors expressed PD-L1.
Also, more patients responded to the Keytruda-chemotherapy than to chemotherapy alone, with an objective response rate (ORR) of 68%. In patients who responded, the median duration of response (DOR) was 18 months for the Keytruda-chemo group and 10.4 months for chemotherapy, with or without bevacizumab.
Not only was this study for first-line advanced cervical cancer, but as mentioned above, it was a confirmatory trial for its accelerated approval for cervical cancer. This allowed the FDA to convert the accelerated approval over to a standard approval.
KEYNOTE-826 enrolled 617 patients with persistent, recurrent or first-line metastatic cervical cancer who had not received chemotherapy except when used concurrently as a radio-sensitizing agent. They were enrolled no matter what their PD-L1 expression was. However, patients were ineligible who had autoimmune disease requiring systemic therapy within two years of treatment or a condition requiring immunosuppression. Patients were randomized by metastatic status at initial diagnosis and their physician decided whether to use bevacizumab and PD-L1 status. Bevacizumab is Genentech’s Avastin.
“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,” said Bradley Monk, 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. “There have been no first-line approvals for women with persistent, recurrent or metastatic cervical cancer in the past seven years. I am excited for today’s approval of a new combination with Keytruda, which offers a new treatment option for appropriate patients.”
Roy Baynes, Merck Research Laboratories’ Senior Vice President and Head of Global Clinical Development and Chief Medical Officer, noted that, “Today’s news is a meaningful step forward, as it offers a new therapeutic option for these patients and reinforces the role of Keytruda in treating certain types of cervical cancers, with a second indication for the disease. The data showing a 36% reduction in the risk of death are compelling, and this approval brings an important new first-line treatment option to women with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1.”
