A Phase 3 Study of Pembrolizumab (Pembro) + Concurrent Chemoradiotherapy (CCRT) for High-Risk Locally Advanced Cervical Cancer (LACC): Safety Findings

Abstract

Purpose/Objective(s)

In ENGOT-cx11/GOG-3047/KEYNOTE-A18 (NCT04221945), pembro + CCRT improved PFS (HR = 0.70 [95% CI = 0.55‒0.89]; P = 0.0020) and showed a favorable trend in OS (HR = 0.73 [95% CI = 0.49‒1.07]) vs placebo (pbo) + CCRT in high-risk LACC at interim analysis 1 (IA1). Here, we report IA1 safety data.

Materials/Methods

Patients (pts) with previously untreated, high-risk LACC (FIGO 2014 stage IB2‒IIB node-positive or stage III‒IVA) were randomized 1:1 to 5 cycles of pembro 200 mg or pbo Q3W + CCRT, then 15 cycles of pembro 400 mg or pbo Q6W. CCRT included 5 cycles (optional 6th dose) of cisplatin 40 mg/m² QW + EBRT followed by brachytherapy. Safety was evaluated in all randomized and treated pts.

Results

Of 1060 randomized pts, 1058 were included in the safety analysis. At data cutoff (Jan 9, 2023), median follow-up was 17.9 mo. AE rates were similar between the treatment arms (see the Table). AEs were more common during the pembro + CCRT combination therapy phase vs pembro monotherapy phase. Exposure-adjusted AE rates generally decreased after 3 mo; hypothyroidism was most common between 3-6 mo with pembro + CCRT. Event rates for genitourinary AEs were < 10.0 events per 100 person-months of exposure during any period.

Conclusion

Pembro + CCRT had manageable safety that was consistent with the known profiles of pembro monotherapy and chemoradiotherapy. Most AEs occurred during the combination therapy phase.