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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

2021; Elsevier BV; Volume: 22; Issue: 5 Linguagem: Inglês

10.1016/s1470-2045(21)00081-4

1474-5488

Andrew Bottomley, Corneel Coens, Justyna Mierzynska, Christian U. Blank, Mario Mandalà, Georgina V. Long, Victoria Atkinson, Stéphane Dalle, Andrew Haydon, Andrey Meshcheryakov, Adnan Khattak, Matteo S. Carlino, Shahneen Sandhu, Susana Puig, Paolo A. Ascierto, James Larkin, Paul Lorigan, Piotr Rutkowski, Dirk Schadendorf, Rutger H.T. Koornstra, Leonel F. Hernandez‐Aya, Anna Maria Di Giacomo, Alfons J.M. van den Eertwegh, Jean‐Jacques Grob, Ralf Gutzmer, Rahima Jamal, Alexander C.J. van Akkooi, Clemens Krepler, Nageatte Ibrahim, Sandrine Marréaud, Michal Kiciński, Stefan Suciu, Caroline Robert, Alexander M.M. Eggermont, Thierry Lesimple, Michele Maio, Gerald P. Linette, Laurent Mortier, Inge Marie Svane, Jacob Schachter, Michael P. Brown, Peter Hersey, Catherine Barrow, Ragini R. Kudchadkar, Caroline Dutriaux, Xinni Song, Pietro Quaglino, Paola Queirolo, Friedegund Meier, Daniil Stroyakovskiy, B. Guillot, Pablo L. Ortiz‐Romero, Lars Bastholt, Claus Garbe, Florent Grange, Peter Mohr, Alain P. Algazi, Oliver Bechter, Micaela Hernberg, Carmen Loquai, Frank Meiß, Vanna Chiarion‐Sileni, Gil Bar‐Sela, Bernard M. Fitzharris, Philippe Saïag, Jean‐Philippe Arnault, Jan‐Christoph Simon, Rosalie Stephens, Jean‐François Baurain, Célèste Lebbe, P. Combemale, Reinhard Dummer, Axel Hauschild, Phillip Parente, Naoya Yamazaki, Mohammed Milhem, M.‐T. Leccia, L. Geoffrois, Lutz Kretschmer, Elaine Dunwoodie, John Walker, Michal Lotem, Daniel Hendler, Andrzej Maćkiewicz, Lidija Kandolf Sekulović, Marcin Dzienis, Geke A.P. Hospers, Marco Siano, Jessica C. Hassel, Pippa Corrie, Maria-Jose Passos, Max Levin, Christoph Höeller, L. Machet, Sigrun Hallmeyer, Ashita Waterston, V. Descamps, Felix Kiecker, Maureen J.B. Aarts, Henrik Schmidt, Ana Raimundo, Marta Nyakas, J.‐P. Lacour, Carola Berking, Pier Francesco Ferrucci, Michael B. Jameson, Kevin Kim, Kenji Yokota, Joseph Kerger, F. Aubin, Gerard Groenewegen, H.W. Kapiteijn, Wolf‐­Henning Boehncke, Jochen Utikal, Richard Casasola, Ernest Marshall, Virginia Ferraresi, Erika Richtig, Suzana Matković, Takashi Inozume, Timothy Crook, Catriona M. McNeil, Yoshio Kiyohara, Marie‐Françoise Avril, Rüdiger Hein, Patrick Terheyden, Paul Nathan, Jun Aoi, Tanja Skyttä, Thomas Jouary, Tatsuya Takenouchi, Oddbjørn Straume, César Martins, Guzel Mukhametshina,

Nonmelanoma Skin Cancer Studies

Background The European Organisation for Research and Treatment of Cancer (EORTC) 1325-MG/KEYNOTE-054 trial in patients with resected, high-risk stage III melanoma demonstrated improved recurrence-free survival with adjuvant pembrolizumab compared with placebo (hazard ratio 0·57 [98·4% CI 0·43–0·74]; p<0·0001). This study reports the results from the health-related quality-of-life (HRQOL) exploratory endpoint. Methods This double-blind, randomised, controlled, phase 3 trial was done at 123 academic centres and community hospitals across 23 countries. Patients aged 18 years or older with previously untreated histologically confirmed stage IIIA, IIIB, or IIIC resected cutaneous melanoma, and an Eastern Cooperative Oncology Group performance status score of 1 or 0 were eligible. Patients were randomly assigned (1:1) using a central interactive voice-response system on the basis of a minimisation technique stratified for stage and geographic region to receive intravenously 200 mg pembrolizumab or placebo. Treatment was administered every 3 weeks for 1 year, or until disease recurrence, unacceptable toxicity, or death. The primary endpoint of the trial was recurrence-free survival (reported elsewhere). HRQOL was a prespecified exploratory endpoint, with global health/quality of 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 registered with 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 the time of this analysis. HRQOL compliance was greater than 90% at baseline, greater than 70% during the first year, and greater than 60% thereafter for both groups. Because of low absolute compliance numbers at later follow-up, the analysis was truncated to week 84. Baseline GHQ scores were similar between groups (77·55 [SD 18·20] in the pembrolizumab group and 76·54 [17·81] in the placebo group) and remained stable over time. The difference in average GHQ score between the two groups over the 2 years was −2·2 points (95% CI −4·3 to −0·2). The difference in average score during treatment was −1·1 points (95% CI −3·2 to 0·9) and the difference in average score after treatment was −2·2 points (−4·8 to 0·4). These differences are within the 5-point clinical relevance threshold for the QLQ-C30 and are therefore clinically non-significant. Interpretation Pembrolizumab does not result in a clinically significant decrease in HRQOL compared with placebo when given as adjuvant therapy for patients with resected, high-risk stage III melanoma. These results support the use of adjuvant pembrolizumab in this setting. Funding Merck Sharp & Dohme.