According to updated results from the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to concurrent chemoradiotherapy provided a statistically significant and clinically meaningful improvement to both overall survival (OS) and time to subsequent progression on after initiation of new anticancer therapy or death from any cause (progression-free survival 2, PSF2).

These results were first presented by Linda Duska, MD, University of Virginia Health, Charlottesville, Virginia, at the Society for Gynecological Oncology (SGO) Annual Meeting on Women’s Cancer.

This phase 3 trial enrolled 1060 patients with newly diagnosed, previously untreated, high-risk, locally advanced cervical cancer. Patients were randomized on a 1-to-1 basis to receive concurrent chemoradiotherapy (CCRT) plus 5 cycles of 200 mg pembrolizumab (n = 529) or placebo (n = 531) every 3 weeks followed by 15 cycles of 400 mg pembrolizumab or placebo every 6 weeks. Patients were stratified by planned external beam radiotherapy type, stage at screening, and planned total radiotherapy dose. The primary end points were PFS and OS with secondary end points including PSF2. At the first interim analysis, it was reported that there was a statistically significant and clinically meaningful improvement in PFS with the addition to pembrolizumab. Based on those results, this combination was approved by the US Food and Drug Administration for patients with stage III to IVA cervical cancer.

At this analysis, with a data cutoff date of January 8, 2024, the median follow-up duration was 29.9 months. The 36-month OS rate was 82.6% in the pembrolizumab arm vs 74.8% in the CCRT alone arm, and median OS was not reached in either arm (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.50 to 0.90; P = .0040). This benefit was seen across most subgroups, including stages IB2 to IIB and stages III to IVA. In the pembrolizumab arm, 15.3% of patients experienced a PSF2 event vs 24.3% in the CCRT alone group, with neither arm reaching a median PFS2 (HR .60; 95% CI, 0.46 to 0.80; P = .0002). Grade ≥3 treatment-related adverse events occurred in 69.1% of the pembrolizumab arm and 61.3% of the CCRT alone arm.

Dr Duska et al concluded, “These data provide further support for pembrolizumab plus CCRT as a new standard of care for this population.”

Source:

Duska L, Xiang Y, Hasegawa K, et al. Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: Overall survival and progression-free survival 2 results from the randomized, double blind, phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study. Presented at 2025 SGO Annual Meeting on Women’s Cancer. March 14-17, 2025; Seattle, WA. Abstract LBA 935279