On October 13, 2021, the FDA announced the approval of pembrolizumab (Keytruda) for use in combination with chemotherapy, with or without bevacizumab, for patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (combined positive score [CPS] >1), as determined by an FDA-approved test.

The approval is based on KEYNOTE-826, a phase III, multicenter, randomized, double-blind, placebo-controlled trial that examined pembrolizumab with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab. The trial enrolled 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who had not been treated with chemotherapy.

Patients were enrolled irrespective of PD-L1 expression status. Patients were randomized (1:1) to one of two treatment groups: pembrolizumab 200 mg plus chemotherapy with or without bevacizumab or placebo plus chemotherapy with or without bevacizumab. Pembrolizumab was continued until disease progression, unacceptable toxicity, or 24 months of treatment.  

The primary efficacy outcome measures were overall survival (OS) and progression-free survival (PFS) assessed by the investigator using RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ. Additional outcome measures were overall response rate (ORR) and duration of response (DoR). For patients with tumors expressing PD-L1 (CPS >1, n = 548), the median OS was not reached (95% CI: 19.8, not reached) in the pembrolizumab arm and was 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).

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 ORRs were 68% (95% CI: 62, 74) and 50% (95% CI: 44, 56) with median DoR of 18.0 and 10.4 months in the pembrolizumab and placebo arms, respectively.  

The most common adverse reactions (>20%) in patients treated with pembrolizumab, chemotherapy, and bevacizumab were peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, and decreased appetite.  

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, stated, "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 (CPS >1)."

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