58 KEYNOTE-826: Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer

Introduction/Background* Pembrolizumab has efficacy in previously treated, PD-L1-positive advanced cervical cancer. KEYNOTE-826 (NCT03635567) was a phase 3, randomised, double-blind trial of pembrolizumab or placebo added to chemotherapy ± bevacizumab for first-line treatment of recurrent, persistent, or metastatic cervical cancer. Methodology Eligible adults had persistent, recurrent, or metastatic cervical cancer not previously treated with systemic chemotherapy and not amenable to curative treatment. Patients were randomised 1:1 to pembrolizumab 200 mg or placebo Q3W for ≤35 cycles added to chemotherapy (paclitaxel plus cisplatin or carboplatin) ± bevacizumab and stratified by metastatic status at diagnosis, planned bevacizumab use, and PD-L1 combined positive score (CPS). Dual primary endpoints were PFS (RECIST v1.1, investigator review) and OS tested sequentially in the CPS ≥1, all-comer, and CPS ≥10 populations. Result(s)* 617 patients were randomized: 308 to pembrolizumab plus chemotherapy (63.6% with bevacizumab) and 309 to placebo plus chemotherapy (62.5% with bevacizumab); 548 (88.8%) patients had CPS ≥1, 317 (51.4%) had CPS ≥10. At the protocol-specified first interim analysis, pembrolizumab plus chemotherapy ± bevacizumab significantly improved PFS in the CPS ≥1 (median, 10.4 vs 8.2 months; HR, 0.62 [95% CI, 0.50–0.77]; P Conclusion* Pembrolizumab plus chemotherapy ± bevacizumab significantly improves OS and PFS in patients with persistent, recurrent, or metastatic cervical cancer. Along with a manageable safety profile, the clinically meaningful survival benefits suggest pembrolizumab plus chemotherapy ± bevacizumab may be a new standard first-line therapy for this population.