Pembrolizumab with chemoradiotherapy in patients with high-risk locally advanced cervical cancer: Final analysis results of the phase 3, randomized, double-blind ENGOT-cx11/GOG-3047/KEYNOTE-A18 study.

LBA5504 Background: Prior results from ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945) showed that pembro + CCRT and then continued after CCRT provided statistically significant and clinically meaningful improvements in OS and PFS vs CCRT alone in pts with newly diagnosed, previously untreated, high-risk LACC. We present the final analysis (FA) results from this study. Methods: Eligible pts with newly diagnosed, previously untreated, high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of lymph node status) were randomized 1:1 to 5 cycles of pembro 200 mg or placebo (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/m 2 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 (<70 Gy vs ≥70 Gy equivalent dose). Primary endpoints are PFS per RECIST version 1.1 by investigator and OS. Results: 1060 pts were randomized to pembro + CCRT (n=529) or pbo + CCRT (n=531). At the protocol-specified FA (Jan 7, 2025, data cutoff), median follow-up was 41.9 mo (range, 24.8-55.0). 86 pts had received post-progression immunotherapy; of those, 64 had received pembro. Pembro + CCRT continued to show clinically meaningful improvements in OS and PFS vs pbo + CCRT (Table). The benefit of pembro + CCRT was generally consistent in prespecified subgroups, including pts with stage IB2-IIB node-positive disease (OS HR=0.92 [95% CI, 0.62-1.38]; PFS HR=0.84 [95% CI, 0.63-1.14]). The grade ≥3 TRAE incidence was 69.5% in the pembro + CCRT group and 61.5% in the pbo + CCRT group. Conclusion: With an additional 12 mo median follow-up, pembro + CCRT continued to show clinically meaningful improvements in OS and PFS vs pbo + CCRT in pts with high-risk LACC and had a manageable safety profile. These data are consistent with the prior interim analysis and provide further support for pembro + CCRT as the new standard of care for this population. Clinical trial information: NCT04221945 . Summary of PFS and OS in ENGOT-cx11/GOG-3047/KEYNOTE-A18. Final Analysis 07JAN25 Interim Analysis 2 08JAN24 Interim Analysis 1 09JAN23 Pembro + CCRT Pbo + CCRT Pembro + CCRT Pbo + CCRT Pembro + CCRT Pbo + CCRT OS, median (95% CI) NR (NR-NR) NR (NR-NR) NR (NR-NR) NR (NR-NR) NR (NR-NR) NR (NR-NR) 36-mo OS 81.8% 74.4% 82.6% 74.8% NR (NR-NR) NR (NR-NR) HR (95% CI) 0.73 (0.57-0.94) 0.67 (0.50-0.90); P =0.0040 0.73 (0.49-1.07); P =0.0541 PFS, median (95% CI) 47.6 (47.6-NR) 47.5 (41.0-NR) NR (NR-NR) NR (32.0-NR) NR (NR-NR) NR (NR-NR) 24-mo PFS 70.6% 59.7% 70.6% 58.6% 67.8% 57.3% HR (95% CI) 0.72 (0.59-0.87) 0.68 (0.56-0.84) 0.70 (0.55-0.89); P =0.0020 NR=not reached.