ESTRO 2024 - Abstract Book

S1125

Clinical - Gynaecology

ESTRO 2024

has shown efficacy and a manageable safety profile in patients with cervical cancer. The ENGOT-cx11/GOG 3047/KEYNOTE-A18 study (ClinicalTrials.gov, NCT04221945) assessed the efficacy and safety of pembrolizumab plus concurrent chemoradiotherapy (CCRT) for patients with high-risk LACC.

Material/Methods:

Eligible patients with newly diagnosed, previously untreated, high-risk LACC (International Federation of Gynecology and Obstetrics 2014 stage IB2 ‒ IIB with node-positive disease or stage III ‒ IVA) were randomized 1:1 to receive 5 cycles of pembrolizumab 200 mg or placebo Q3W plus CCRT, then 15 cycles of pembrolizumab 400 mg or placebo Q6W. The CCRT regimen included 5 cycles (with an optional 6th dose) of cisplatin 40 mg/m 2 QW plus EBRT followed by brachytherapy. Patients were stratified by planned EBRT type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), stage at screening (stage IB2 ‒ IIB vs III ‒ IVA), and planned total radiotherapy dose (<70 Gy vs ≥70 Gy equivalent dose in 2-Gy fractions [EQD2]). Primary endpoints were PFS per RECIST version 1.1 by investigator or histopathologic confirmation and OS.

Results:

1060 patients were randomized to pembrolizumab plus CCRT (n = 529) or placebo plus CCRT (n = 531). At the protocol-specified first interim analysis (data cutoff, January 9, 2023), median follow-up was 17.9 (range, 0.9 ‒ 31.0) months. Patients received a median of 11 (range, 1 ‒ 20) cycles of pembrolizumab or placebo and 5 (range, 1 ‒ 7) cycles of cisplatin in both treatment groups. Radiation treatment was completed in 518 (97.9%) patients in the pembrolizumab plus CCRT group and 522 (98.3%) patients in the placebo plus CCRT group for an overall median treatment duration of 52.0 (range, 12.0 ‒ 139.0) days and 52.0 (2.0 ‒ 166.0) days, respectively. For EBRT, patients predominantly received IMRT or VMAT (pembrolizumab plus CCRT, 89.2%; placebo plus CCRT, 87.5%) compared with non-IMRT or non-VMAT (10.8% and 12.5%, respectively). For brachytherapy, most patients received volume based brachytherapy (pembrolizumab plus CCRT, 88.2%; placebo plus CCRT, 86.8%) compared with point A brachytherapy (9.3% and 8.2%, respectively); brachytherapy was not started in 2.5% and 5.0% of patients, respectively. Brachytherapy techniques included high-dose rate (HDR; pembrolizumab plus CCRT, 94.6%; placebo plus CCRT, 94.3%) and pulsed-dose rate (PDR) or low-dose rate (LDR; 2.9% and 0.8%, respectively). CCRT exposure in patients who completed radiation treatment is detailed in the table. Pembrolizumab plus CCRT significantly improved PFS versus placebo plus CCRT (hazard ratio, 0.70 [95% CI, 0.55 ‒ 0.89; P = 0.0020). 24-month PFS rates were 67.8% versus 57.3%, respectively; median PFS was not reached in either group. The PFS benefit was generally consistent across all prespecified subgroups. With only 103 events (42.9% maturity), the addition of pembrolizumab to CCRT showed a favorable trend in OS (hazard ratio, 0.73 [95% CI, 0.49 ‒ 1.07]); these data have not crossed the boundary of statistical significance at this interim analysis. The percentage of patients experiencing treatment-related AEs was lower during the monotherapy phase compared with the combination therapy phase in both the pembrolizumab plus CCRT (72.7% vs 94.5%) and placebo plus CCRT (60.0% vs 95.7%) groups. The safety profiles were generally consistent with the known profiles of pembrolizumab monotherapy and chemoradiotherapy. There were no safety concerns, and AEs were manageable with the combination of pembrolizumab plus CCRT. In the pembrolizumab plus CCRT group, treatment-related AEs during combination therapy resulted in the discontinuation of cisplatin in 10.4% of patients, pembrolizumab in 1.5% of patients, EBRT in 0% of patients, and brachytherapy in 0% of patients. The corresponding treatment-related AE discontinuation rates in the placebo plus CCRT group were 10.8%, 0.9%, 0%, and 0.2%, respectively.