161 Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: the randomized, double-blind, phase 3 ENGOT-Cx11/GOG-3047/KEYNOTE-A18 study

Introduction/Background Pembrolizumab has shown efficacy in patients with cervical cancer. The effect of chemoradiotherapy may be enhanced by immunotherapy. ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945) assessed efficacy and safety of pembrolizumab + concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC). Methodology Eligible patients with newly diagnosed, previously untreated, high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA) were randomized 1:1 to receive 5 cycles of pembrolizumab 200 mg or placebo Q3W + CCRT, then 15 cycles of pembrolizumab 400 mg or placebo Q6W. The CCRT regimen included 5 cycles (with optional sixth dose) of cisplatin 40 mg/m2 Q1W + EBRT then brachytherapy. Patients were stratified by planned EBRT type (IMRT/VMAT vs non-IMRT/non-VMAT), stage at screening (stage IB2-IIB vs III-IVA) and planned total radiotherapy dose. Primary endpoints were PFS per RECIST v1.1 by investigator and OS. Results 1060 patients were randomized to pembrolizumab+CCRT (n=529) or placebo+CCRT (n=531). At the protocol-specified first interim analysis (January 9, 2023, data cutoff), median follow-up was 17.9 mo (range, 0.9–31.0). Pembrolizumab+CCRT showed a statistically significant improvement in PFS vs placebo+CCRT. 24-mo PFS was 67.8% with pembrolizumab+CCRT vs 57.3% with placebo+CCRT; median PFS was not reached in either group (HR=0.70 [95% CI, 0.55–0.89; P=0.0020]); results were consistent across all prespecified subgroups. With only 103 events (42.9% maturity), the addition of pembrolizumab to CCRT showed a favorable trend in OS (HR=0.73 [95% CI, 0.49–1.07]); these data have not crossed the boundary of statistical significance. Grade ≥3 TRAE incidence was 67.0% in the pembrolizumab+CCRT group and 60.0% in the placebo+CCRT group. Conclusion Pembrolizumab+CCRT showed a statistically significant and clinically meaningful improvement in PFS and a favorable trend in OS compared with placebo+CCRT in patients with high-risk locally advanced cervical cancer and had a manageable safety profile. These data suggest pembrolizumab+CCRT can be considered as a new standard of care for this population. Disclosures Disclosures are provided via the ESGO COI Disclosure forms.