The Food and Drug Administration (FDA) has approved Keytruda (pembrolizumab) 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 or greater) as determined by an FDA-approved test.
The approval was based on data from the multicenter, randomized, double-blind, placebo-controlled phase 3 KEYNOTE-826 trial (ClinicalTrials.gov Identifier: NCT03635567) that evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy (paclitaxel plus cisplatin or paclitaxel plus carboplatin), with or without bevacizumab, in 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who had not been treated with chemotherapy except when used concurrently as a radiosensitizing agent.
Patients were randomly assigned 1:1 to receive pembrolizumab 200mg plus chemotherapy or placebo plus chemotherapy, with or without bevacizumab, until disease progression, unacceptable toxicity, or 24 months of treatment. The coprimary end points were overall survival and progression-free survival as assessed using RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Key secondary end points were objective response rate and duration of response.
Among 548 patients with tumors expressing PD-L1 with CPS greater than or equal to 1, results showed that median overall survival 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 0.64; 95% CI, 0.50-0.81; 1-sided P =.0001). Median progression-free survival was 10.4 months (95% CI, 9.7-12.3) in the pembrolizumab arm compared with 8.2 months (95% CI, 6.3-8.5) in the placebo arm (hazard ratio 0.62; 95% CI, 0.50-0.77; 1-sided P <.0001).
The objective response rates were 68% (95% CI, 62-74) and 50% (95% CI, 44-56) in the pembrolizumab and placebo groups, respectively. Median duration of response was 18.0 months for pembrolizumab vs 10.4 months for placebo.
Keytruda also received regular approval as a single agent for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1 or greater) as determined by an FDA-approved test. In June 2018, the FDA granted accelerated approval for this indication, along with the companion diagnostic, PD-L1 IHC 22C3 pharmDx.
- FDA approves pembrolizumab combination for the first-line treatment of cervical cancer. News release. US Food and Drug Administration. Accessed October 13, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-combination-first-line-treatment-cervical-cancer.
- Keytruda. Package insert. Merck; 2021. Accessed October 13, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s121s122lbl.pdf.