Article Text
Abstract
Introduction The phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study (NCT04221945) evaluated pembrolizumab+concurrent chemoradiotherapy (CCRT) followed by pembrolizumab versus placebo+CCRT followed by placebo in patients with high-risk LACC. At interim analysis 1 (IA1), addition of pembrolizumab significantly improved PFS (HR, 0.70 [95% CI, 0.55–0.89]; P=0.0020) with a favorable trend for improved OS (HR, 0.73 [95% CI, 0.49–1.07]) in the intention-to-treat population. We present updated PFS and safety data from IA2 for patients enrolled in Asia.
Methods Patients had newly diagnosed, high-risk LACC (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of lymph node status). Patients were randomized (1:1) to receive 5 cycles of pembrolizumab 200mg or placebo Q3W plus CCRT, then 15 cycles of pembrolizumab 400mg or placebo Q6W. CCRT included 5 cycles (optional 6th dose) of cisplatin 40mg/m2 QW+EBRT, then brachytherapy. Primary endpoints were PFS per RECISTv1.1 by investigator assessment or histopathologic confirmation and OS.
Results 299 patients were enrolled in Asia (pembrolizumab+CCRT, n=153; placebo+CCRT, n=146). Median follow-up at database cutoff (January 8, 2024) was 31.2 (range, 12.8–43.0) months. Median PFS was not reached in either group; HR favored pembrolizumab+CCRT (0.61 [95% CI, 0.40–0.93]). 24-month PFS rate was 78.3% and 64.2% with pembrolizumab+CCRT and placebo+CCRT, respectively. No grade 5 treatment-related AEs occurred. Grade 3/4 treatment-related AE incidence was 78.9% and 78.1%, respectively. Immune-mediated AE incidence was 46.7% and 15.1% (grade 1/2, 42.1% and 13.7%).
Conclusion/Implications At IA2, pembrolizumab+CCRT continued to demonstrate PFS benefit versus placebo+CCRT, with manageable safety in patients with high-risk LACC enrolled in Asia.