Health-related quality-of-life results for pembrolizumab versus placebo after complete resection of high-risk stage III melanoma from the EORTC 1325-MG/Keynote 054 trial: An international randomized double-blind phase III trial

Abstract

Background: The EORTC 1325‐MG/Keynote 054 trial demonstrated prolonged recurrence‐ free survival with adjuvant pembrolizumab compared to placebo (hazard ratio = 0.57; P<0.001. Eggermont et al, NEJM, 2018). Incidence of adverse events grades 3 or higher related to treatment were higher in the pembrolizumab arm (14.7%) than the placebo arm (3.4%). Here we report results from the health‐related quality of life (HRQoL) exploratory endpoint. Methods: A total of 1019 patients with histologically confirmed, cutaneous melanoma metastatic to a lymph node, classified as stage IIIA, IIIB or IIIC were randomized after complete resection to receive 200 mg pembrolizumab (514 patients) or placebo (505 patients). Treatment was administered every 3 weeks for 1 year, or until disease recurrence or unacceptable toxicity. All enrolled patients were required to complete a HRQoL questionnaire at baseline and every 12 weeks (during 2 years after randomization). The primary HRQoL outcome was global health/QoL (GHQ) as measured by the EORTC QLQ‐C30. All other scales from this questionnaire were secondary. Scores were compared according to the average score per patient overall, during treatment and after treatment. Results: HRQoL compliance was>90% at baseline, >70% during the first year and >60% thereafter for both arms. Data attrition limited the analyses to week 84 (19 months). Baseline GHQ scores were similar between arms at 77 points and remained stable over time. The average GHQ score was 2.2 points (95% CI: 4.3‐0.2), 1.1 points (95% CI: 3.2 ‐ ‐0.9) and 2.2 points (95% CI: 4.8 ‐ ‐0.4) lower in the pembrolizumab arm compared to placebo for the average overall, during and after treatment respectively. These differences are within 5 point clinical relevance threshold for the QLQ‐C30. Results from the secondary scales revealed a similar pattern with scores stable over time and treatment differences never reaching the 5 point threshold. Conclusions: Pembrolizumab maintains health‐related quality of life compared to placebo, when given as adjuvant therapy for patients with resected high‐risk stage III melanoma.