Patient-reported outcomes from the phase III, randomized, double-blind, placebo-controlled ENGOT-cx11/GOG-3047/KEYNOTE-A18 Study of pembrolizumab plus concurrent chemoradiotherapy among patients with high-risk, locally advanced cervical cancer.

Abstract

Objectives: The phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study (NCT04221945) evaluates pembrolizumab + concurrent chemoradiotherapy (CCRT) versus placebo + CCRT among patients with high-risk locally advanced cervical cancer (LACC; FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA). At stage IA1 (data cutoff, January 9, 2023), there was a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with the addition of pembrolizumab to CCRT (HR: 0.70; 95 % CI: 0.55-0.89; P = 0.002) and a favorable trend in overall survival (OS) improvement (data not mature). We reported prespecified patient-reported outcome (PRO) analyses from the study. Method(s): Eligible patients were randomized 1:1 to receive 5 cycles of pembrolizumab 200 mg Q3W + CCRT (cisplatin 40 mg/m2 plus external beam radiation therapy [EBRT] followed by brachytherapy) followed by 15 cycles of pembrolizumab 400 mg Q6W or to 5 cycles of placebo Q3W + CCRT followed by 15 cycles of placebo Q6W. A 6th optional dose of cisplatin could be administered per local practice. PRO instruments included EORTC quality of life core 30 (QLQ-C30), EORTC Cervical Cancer module (QLQ-CX24), and EuroQol EQ-5D-5L visual analog scale (VAS), administered at each treatment cycle. Changes from baseline to week 36 (last time with completion/compliance >=60 %/>=80 %) in QLQ-C30 global health status/quality of life (GHS/QoL) and physical functioning (PF) and the QLQ-CX24 symptom-experience scale were secondary study endpoints. Other PRO analyses were exploratory endpoints. PRO analyses included patients who received >=1 dose of study treatment and had >=1 post-baseline PRO assessment. Per protocol, PROs were classified as improved based on a >= 10-point change (QLQ-C30, QLQ-CX24) or >= 7-point change (EQ-5D-5L). No alpha was assigned to PRO analyses. Result(s): Of 1060 patients in the intent-to-treat population, 1008 were included in PRO analyses (pembrolizumab + CCRT, n = 502; placebo + CCRT, n = 506). Completion/compliance at week 36 for the QLQ-C30 was 62.2 %/96.0 % for pembrolizumab + CCRT and 61.5 %/96.0 % for placebo + CCRT. At baseline, PRO scores were similar between treatment groups. In both arms, QLQ-C30 GHS/QoL and QLQ-C30 PF and EQ-5D-5L VAS scores decreased from baseline at weeks 3 and 6 but improved relative to baseline at week 12 and subsequent weeks. A similar number of patients had improved/stable scores for the QLQ-C30 GHS/QoL (75.7 % vs 75.3 %), QLQ-C30 PF (76.5 % vs 76.5 %), QLQ-CX24 symptom experience (84.7 % vs 85.1 %) and EQ-5D-5L VAS (73.3 % vs 75.6 %). There were no clinically meaningful between-group differences in changes in PRO scores from baseline to week 36 for QLQ-C30 GHS/QoL, QLQ-C30 PF, QLQ-CX24 symptom experience, or EQ-5D-5L VAS (Table). Conclusion(s): Improvement in PFS with the addition of pembrolizumab to CCRT among patients with high-risk LACC was accompanied by QoL changes similar to those in the placebo + CCRT group. These results support pembrolizumab plus CCRT as a new standard of care for patients with high-risk LACC and support the positive benefit-risk profile of this combination. [Formula presented]Copyright © 2024