Dr Randall on PROs With Pembrolizumab Plus Chemoradiotherapy in Cervical Cancer

Leslie M. Randall, MD, MAS, professor, division head, Department of Obstetrics and Gynecology – Gynecologic Oncology, Virginia Commonwealth University School of Medicine Obstetrics and Gynecology, discusses findings from a patient-reported outcomes (PROs) analysis of the phase 3 ENGOT-cx11/GOG 3047/KEYNOTE-A18 trial (NCT04221945) of pembrolizumab (Keytruda) plus concurrent chemoradiotherapy in patients with high-risk, locally advanced cervical cancer.

At the first interim analysis, with a data cutoff of January 9, 2023, the KEYNOTE-A18 trial demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with pembrolizumab plus concurrent chemoradiotherapy vs placebo plus concurrent chemoradiotherapy (HR, 0.70; 95% CI, 0.55-0.89; P = .002). These PFS findings warranted the evaluation of additional efficacy measures, including PRO benefit, in a prespecified analysis, Randall says.

The PRO analysis used the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire 30 (EORTC-QLQ-C30), the EORTC QLQ cervical cancer model (EORTC-QLQ-CX24), and the EQ-5D-5L Visual Analogue Scale (VAS).

At week 36, the EORTC-QLQ-C30 completion and compliance rates were 62.2% and 96.0%, respectively, in the pembrolizumab arm (n = 502) vs 61.5% and 96.0%, respectively, in the placebo arm (n = 506). Patients in both the pembrolizumab and placebo arms experienced an initial decrease in EQ-5D-5L VAS scores and EORTC-QLQ-C30 global health status (GHS)/quality of life (QOL) and physical functioning subscale scores at weeks 3 and 6, but by week 12 and at all subsequent weeks, these scores improved relative to baseline. No meaningful differences were observed in score changes from baseline to week 36, as well as the number of patients with overall improved or stable scores, for EORTC-QLQ-C30 GHS/QOL, EORTC-QLQ-C30 physical functioning subscale, EORTC-QLQ-CX24 symptom experience, or EQ-5D-5L VAS.

This robust PRO analysis demonstrated high completion and compliance rates with pembrolizumab plus concurrent chemoradiotherapy, indicating that the combination did not induce a QOL detriment vs concurrent chemoradiotherapy alone in the KEYNOTE-A18 trial population, Randall explains. These findings support the addition of pembrolizumab to concurrent chemoradiotherapy for patients with high-risk, locally advanced cervical cancer, Randall concludes.