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.

Bottomley A, Coens C, Mierzynska J, Blank CU, Mandalà M, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Puig S, Ascierto PA, Larkin J, Lorigan PC, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJ, Grob JJ, Gutzmer R, Jamal R, van Akkooi AC, Krepler C, Ibrahim N, Marreaud S, Kicinski M, Suciu S, Robert C, Eggermont AM, Lesimple T, Maio M, Linette G, Mortier L, Svane IM, Schachter J, Brown M, Hersey P, Barrow C, Kudchadkar R, Dutriaux C, Song X, Quaglino P, Queirolo P, Meier F, Stroyakovskiy D, Guillot B, Romero PLO, Bastholt L, Garbe C, Grange F, Mohr P, Algazi A, Bechter O, Hernberg M, Loquai C, Meiss F, Chiarion Sileni V, Bar-Sela G, Fitzharris B, Saiag P, Arnault JP, Simon JC, Stephens R, Baurain JF, Lebbe C, Combemale P, Dummer R, Hauschild A, Parente P, Yamazaki N, Milhem M, Leccia MT, Geoffrois L, Kretschmer L, Dunwoodie E, Walker J, Lotem M, Hendler D, Mackiewicz A, Sekulovic L, Dzienis M, Hospers GA, Siano M, Hassel J, Corrie P, Passos MJ, Levin M, Hoeller C, Machet L, Hallmeyer S, Waterston A, Descamps V, Kiecker F, Aarts M, Schmidt H, Raimundo A, Nyakas M, Lacour JP, Berking C, Ferrucci PF, Jameson M, Kim K, Yokota K, Kerger J, Aubin F, Groenewegen G, Kapiteijn H, Boehncke WH, Utikal J, Casasola R, Marshall E, Ferraresi V, Richtig E, Matkovic S, Inozume T, Crook T, McNeil C, Kiyohara Y, Avril MF, Hein R, Terheyden P, Nathan P, Aoi J, Skytta T, Jouary T, Takenouchi T, Straume O, Martins C, Mukhametshina G (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 22

Pages Range: 655-664

Journal Issue: 5

DOI: 10.1016/S1470-2045(21)00081-4

Abstract

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.

Involved external institutions

European Organisation for Research and Treatment of Cancer (EORTC) Belgium (BE) Netherlands Cancer Institute (NKI) Netherlands (NL) Merck & Co., Inc. / Merck Sharp & Dohme Corp (MSD) United States (USA) (US) Institut Gustave-Roussy France (FR) Università degli Studi di Perugia Italy (IT) University of Sydney (USYD) Australia (AU) University of Queensland Australia (AU) Hospices Civils de Lyon (CHU) France (FR) The Alfred Hospital Australia (AU) N.N. Blokhin Russian Cancer Research Center / Российский онкологический научный центр им. Н. Н. Блохина Russian Federation (RU) Fiona Stanley Hospital Australia (AU) Peter MacCallum Cancer Centre Australia (AU) Hospital Clínic de Barcelona Spain (ES) Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" Italy (IT) Royal Marsden Hospital / The Royal Marsden NHS Foundation Trust United Kingdom (GB) Christie NHS Foundation Trust United Kingdom (GB) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Universitätsklinikum Essen Germany (DE) Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC) Netherlands (NL) Washington University in St. Louis United States (USA) (US) Azienda ospedaliero-universitaria Senese Italy (IT) Amsterdam University Medical Centers (Amsterdam UMC) / Amsterdam Universitair Medische Centra Netherlands (NL) Aix-Marseille University / Aix-Marseille Université France (FR) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Centre hospitalier de l'Université de Montréal (CHUM) Canada (CA) Princess Máxima Center Netherlands (NL)

How to cite

APA:

Bottomley, A., Coens, C., Mierzynska, J., Blank, C.U., Mandalà, M., Long, G.V.,... Mukhametshina, G. (2021). 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. Lancet Oncology, 22(5), 655-664. https://doi.org/10.1016/S1470-2045(21)00081-4

MLA:

Bottomley, Andrew, et al. "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." Lancet Oncology 22.5 (2021): 655-664.

BibTeX: Download