Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): health-related quality-of-life results from a double-blind, randomised, controlled, phase 3 trial
Mené dans 23 pays sur 1 019 patients atteints d'un mélanome de stade III ayant été réséqué, cet essai de phase III évalue l'intérêt, du point de vue de la qualité de vie, du pembrolizumab en traitement adjuvant (durée médiane de suivi : 15,1 mois)
Résumé en anglais
Background : The European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054trial in patients with resected, high-risk stage III melanoma demonstrated improvedrecurrence-free survival with adjuvant pembrolizumab compared with placebo (hazardratio 0·57 [98·4% CI 0·43–0·74]; p<0·0001). This study reports the results from thehealth-related quality-of-life (HRQOL) exploratory endpoint.
Methods : This double-blind, randomised, controlled, phase 3 trial was done at 123 academiccentres and community hospitals across 23 countries. Patients aged 18 years or olderwith previously untreated histologically confirmed stage IIIA, IIIB, or IIIC resectedcutaneous melanoma, and an Eastern Cooperative Oncology Group performance status scoreof 1 or 0 were eligible. Patients were randomly assigned (1:1) using a central interactivevoice-response system on the basis of a minimisation technique stratified for stageand geographic region to receive intravenously 200 mg pembrolizumab or placebo. Treatmentwas administered every 3 weeks for 1 year, or until disease recurrence, unacceptabletoxicity, or death. The primary endpoint of the trial was recurrence-free survival(reported elsewhere). HRQOL was a prespecified exploratory endpoint, with global health/qualityof life (GHQ) over 2 years measured by the EORTC QLQ-C30 as the primary analysis.Analyses were done in the intention-to-treat population. This study is registeredwith ClinicalTrials.gov, NCT02362594, and EudraCT, 2014-004944-37, and long-term follow-up is ongoing.
Findings : Between Aug 26, 2015, and Nov 14, 2016, 1019 patients were assigned to pembrolizumab(n=514) or placebo (n=505). Median follow-up was 15·1 months (IQR 12·8–16·9) at thetime of this analysis. HRQOL compliance was greater than 90% at baseline, greaterthan 70% during the first year, and greater than 60% thereafter for both groups. Becauseof low absolute compliance numbers at later follow-up, the analysis was truncatedto week 84. Baseline GHQ scores were similar between groups (77·55 [SD 18·20] in thepembrolizumab group and 76·54 [17·81] in the placebo group) and remained stable overtime. The difference in average GHQ score between the two groups over the 2 yearswas −2·2 points (95% CI −4·3 to −0·2). The difference in average score during treatmentwas −1·1 points (95% CI −3·2 to 0·9) and the difference in average score after treatmentwas −2·2 points (−4·8 to 0·4). These differences are within the 5-point clinical relevancethreshold for the QLQ-C30 and are therefore clinically non-significant.
Interpretation : Pembrolizumab does not result in a clinically significant decrease in HRQOL comparedwith placebo when given as adjuvant therapy for patients with resected, high-riskstage III melanoma. These results support the use of adjuvant pembrolizumab in thissetting.
