Saturday, July 13, 202410:30 AM - 11:30 AM GPP01 Presentation Time: 10:30 AM

Abstract

Purpose

ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945) evaluated pembro + CCRT in patients (pts) with high-risk LACC.

Materials and Methods

Pts with 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 pembro 200 mg or placebo (pbo) Q3W + CCRT then 15 cycles of pembro 400 mg or pbo Q6W. CCRT was 5 cycles (optional 6th dose) of cisplatin 40 mg/m² QW + EBRT then brachytherapy. Primary endpoints were PFS per RECIST v1.1 by investigator or histopathologic confirmation and OS.

Results

1060 pts were randomized to pembro + CCRT (n = 529) or pbo + CCRT (n = 531). At IA1 (data cutoff: Jan 9, 2023), median follow-up was 17.9 mo. Pts received a median of 11 cycles of pembro or pbo and 5 cycles of cisplatin in both arms. Most pts completed radiation treatment (pembro + CCRT, 97.9%; pbo + CCRT, 98.3%); overall median treatment duration was 52 d in both arms. Table 1 summarizes the CCRT treatment. Pembro + CCRT improved PFS vs pbo + CCRT (HR 0.70 [95% CI 0.55‒0.89]; P = 0.0020). Median PFS was not reached in either arm. PFS benefit was generally consistent across prespecified subgroups. With only 103 events (42.9% maturity), pembro + CCRT had a favorable trend in OS (HR 0.73 [95% CI 0.49‒1.07]). Treatment-related AEs (TRAEs) were less common in the pembro monotherapy phase (72.7%) vs pembro + CCRT combination therapy phase (94.5%); results in the pbo arm were 60.0% vs 95.7%. Safety profiles were consistent with the known profiles of pembro monotherapy and chemoradiotherapy.

Conclusions

Pembro + CCRT showed a statistically significant and clinically meaningful improvement in PFS and a favorable trend in OS vs pbo + CCRT in pts with high-risk LACC. Pembro + CCRT had manageable safety, with most TRAEs occurring during the combination phase of therapy. Pembro + CCRT has potential as a new standard of care for this high-risk population.