Abstract
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.MethodologyEligible 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<0.001), all-comer (10.4 vs 8.2 months; 0.65 [0.53–0.79]; P<0.001), and CPS ≥10 (10.4 vs 8.1 months; 0.58 [0.44–0.77]; P<0.001) populations. OS was also significantly improved in the CPS ≥1 (median, not reached [NR] vs 16.3 months; HR, 0.64 [95% CI, 0.50–0.81]; P<0.001), all-comer (24.4 vs 16.5 months; 0.67 [0.54–0.84]; P<0.001), and CPS ≥10 (NR vs 16.4 months; 0.61 [0.44–0.84]; P=0.001) populations. Benefits were seen in the with and without bevacizumab subgroups. The incidence of grade ≥3 AEs was 81.8% in the pembrolizumab arm and 75.1% in the placebo arm. Anaemia and neutropenia were the most common grade ≥3 AEs (30.3% vs 26.9% and 12.4% vs 9.7%, respectively).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.