Multinational phase 3 trial of pembrolizumab plus chemoradiotherapy followed by pembrolizumab for high-risk locally advanced cervical cancer

Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy (CRT) might be enhanced by immunotherapy. The multinational (176 centers in 30 countries) phase 3 KEYNOTE-A18 trial evaluated addition of pembrolizumab to CRT in locally advanced cervical cancer. The study randomized patients with newly diagnosed, high risk, locally advanced cervical cancer to 5 cycles pembrolizumab-CRT (n=529) or placebo-CRT (n=531) followed by 15 cycles of pembrolizumab or placebo. Progression-free rates at 24 months were 68% in the pembrolizumab-CRT group versus 57% in the placebo-CRT group (HR 0.70; p=0.0020). Overall survival rates at 24 months were 87% versus 81% (HR 0.73; 95% CI 0.49-1.07). Grade 3 or higher adverse event rates were 75% in the pembrolizumab-CRT group and 69% in the placebo-CRT group. The authors conclude that pembrolizumab plus CRT significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer.