NEW YORK – The US Food and Drug Administration on Wednesday approved pembrolizumab (Merck's Keytruda) combined with chemotherapy, with or without bevacizumab (Roche's Avastin), as a first-line treatment for advanced cervical cancer patients with PD-L1-expressing tumors.
To be eligible for treatment, advanced cervical cancer patients must have a PD-L1 expression combined positive score of at least one.
In addition to approving this front-line pembrolizumab-chemo-bevacizumab regimen for patients whose cervical cancers are recurrent, persistent, or metastatic, the agency also converted a prior accelerated approval into regular approval for single-agent pembrolizumab as a second-line treatment for patients who had progressed on chemotherapy. Merck received accelerated approval for the later-line indication in June 2018, at which time the FDA also approved Agilent Technologies' Dako PD-L1 IHC 22C3 pharmDx test as a companion diagnostic to identify treatment-eligible patients with PD-L1-positive tumors.
The FDA approved the latest indication based on the results of the Phase III Keynote-826 trial, in which 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who hadn't received prior chemo were randomized to receive either pembrolizumab and chemotherapy with or without bevacizumab, or a placebo and chemotherapy with or without bevacizumab. Patients were enrolled regardless of PD-L1 expression status, but among those with PD-L1-positive tumors, the median overall survival was not yet reached for patients in the immune checkpoint inhibitor arm, versus 16.3 months in the placebo arm. The median progression-free survival was 10.4 months and 8.2 months for the pembrolizumab-containing and placebo-containing regimens, respectively.
The Keynote-826 data also supported FDA's full approval of the second-line single-agent pembrolizumab indication. The agency had relied on data from the Keynote-158 for its original accelerated approval, which showed an objective response rate of 14 percent in 77 patients.