LBA38 Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: A randomized, double-blind, phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study

Pembrolizumab (pembro) has shown efficacy in patients (pts) with cervical cancer. The effect of chemoradiotherapy may be enhanced by immunotherapy. ENGOT-cx11/GOG-3047/KEYNOTE-A18(NCT04221945) assessed the efficacy and safety of pembro + concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer. Eligible pts with newly diagnosed, previously untreated, high-risk locally advanced cervical cancer (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA) were randomized 1:1 to receive 5 cycles of pembro 200 mg or pbo Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. The CCRT regimen included 5 cycles (with optional 6th dose) of cisplatin 40 mg/m2 Q1W + EBRT then brachytherapy. Pts were stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), stage at screening (stage IB2-IIB vs III-IVA) and planned total radiotherapy dose. Primary endpoints were PFS per RECIST version 1.1 by investigator and OS. 1060 pts were randomized to pembro + CCRT (n=529) or pbo + 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). Pembro + CCRT showed a statistically significant improvement in PFS vs pbo + CCRT. 24-mo PFS was 67.8% with pembro + CCRT vs 57.3% with pbo + 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 pembro 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 pembro + CCRT group and 60.0% in the pbo + CCRT group. Pembro + CCRT showed a statistically significant and clinically meaningful improvement in PFS and a favorable trend in OS compared with pbo + CCRT in pts with high-risk locally advanced cervical cancer and had a manageable safety profile. These data suggest pembro + CCRT can be considered as a new standard of care for this population.