On October 13, 2021, the FDA accelerated the approval of pembrolizumab (Keytruda; Merck), in combination with chemotherapy, with or without bevacizumab (Avastin), for the treatment of patients with persistent, recurrent, or metastatic cervical cancer who have not received chemotherapy and whose tumors express PD-L1 ≥1%, as determined by an FDA-approved test.
At the same time, the FDA also granted regular approval to pembrolizumab as a single agent for patients with recurrent or metastatic cervical cancer whose disease progressed during or after chemotherapy and PD-L1 expression ≥1%, as determined by an FDA-approved test. In June 2018, the FDA accelerated the approval of this indication to pembrolizumab.
The approval of first-line pembrolizumab plus chemotherapy indication was based on the KEYNOTE-826 study, a multicenter, randomized, double-blind, placebo-controlled clinical trial. The study included 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who had not received chemotherapy. Patients were enrolled regardless of a PD-L1 expression status. Patients were randomized in a 1:1 ratio to pembrolizumab plus paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab, or to placebo plus chemotherapy, with or without bevacizumab. Pembrolizumab therapy continued until disease progression, unacceptable adverse events, or completion of 24-month treatment.
The main efficacy measures were overall survival (OS) and progression-free survival (PFS). Secondary measures were objective response rate (ORR) and duration of response (DOR).
For the 548 patients with tumors expressing PD-L1 ≥1%, the median OS was not reached (NR; 95% confidence interval [CI], 19.8-NR) in the pembrolizumab arm versus 16.3 months (95% CI, 14.5-19.4) in the placebo arm (hazard ratio [HR], 0.64; 95% CI, 0.50-0.81; 1-sided P = .0001). The median PFS was 10.4 months (95% CI, 9.7-12.3) in the pembrolizumab arm and 8.2 months (95% CI, 6.3-8.5) in the placebo arm (HR, 0.62; 95% CI, 0.50-0.77; 1-sided P <.0001). The ORR was 68% and 50%, and the median DOR was 18 months and 10.4 months, respectively.
The most common (≥20%) adverse reactions in the pembrolizumab arm were peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, and decreased appetite.