LBA44 - Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: Long-term quality of life analysis results of the EORTC 1325-MG/Keynote-054 double-blinded phase III trial

Background

Adjuvant pembrolizumab significantly reduces the risk of metastasis after complete resection in high-risk stage III melanoma (Eggermont et al, TLO, 2021), which may reduce exposure to new treatments, deterioration of physical functioning and global quality of life (QOL). Yet, pembrolizumab may cause long-term toxicities, negatively affecting QOL. The main aim of this analysis is to investigate long-term QOL in the EORTC 1325-MG/Keynote-054 double-blinded trial.d trial.

Methods

Between Aug 2015 and Nov 2016, 1019 patients with resected high-risk stage III melanoma were randomized to pembrolizumab 200 mg or placebo every 3 weeks for a total of 18 doses. QLQ-C30 was administered at baseline, every 12 weeks during the first 2 years and then every 6 months until 4 years from randomization. Long-term QOL was defined as the average QOL between 2 and 4 years from randomization. The primary endpoints were the change from baseline to long-term global QOL and physical functioning scales. A difference >5 points between the treatment arms was deemed as clinically relevant.

Results

The compliance was 93% at baseline and 60-90% thereafter. The mean change from baseline to long-term global QOL was -0.56 (95% CI -2.33, 1.22) in the pembrolizumab and 1.63 (95% CI -0.12, 3.38) in the placebo arm; the treatment difference was -2.19 (95% CI -4.65, 0.27), P=0.08. The mean change from baseline to long-term physical functioning was -0.46 (95% CI -1.69, 0.77) in the pembrolizumab and 0.10 (95% CI -1.14, 1.34) in the placebo arm; the treatment difference was -0.56 (95% CI -2.31, 1.19), P=0.53. The differences regarding role, emotional, cognitive, and social functioning, and fatigue were neither statistically significant nor clinically relevant. Immune-related adverse events were not associated with clinically relevant changes in the investigated scales. Distant metastasis was associated with a clinically relevant deterioration in long-term global QOL, role and social functioning, and fatigue.

Conclusions

There were no clinically relevant differences regarding long-term global QOL and physical functioning between the treatment arms.

Clinical trial identification

NCT02362594; EudraCT 2014-004944-37.

Editorial acknowledgement

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

M. Kicinski: Financial Interests, Institutional, Funding: Merck/MSD, Pierre Fabre; Financial Interests, Institutional, Research Grant: MSD. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Merck Sharpe & Dohme (Australia) Pty Limited, Novartis Pharma AG, OncoSec Medical Australia, Pierre Fabre, Provectus Australia, Qbiotics Group Limited, Regeneron Pharmaceuticals Inc; Financial Interests, Personal, Advisory Board, Consultant Advisor: Highlight Therapeutics S.L. M. Mandala: Financial Interests, Personal, Advisory Board: MSD, Novartis, Sanofi, BMS, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sun Pharma. V.G. Atkinson: Financial Interests, Personal, Advisory Board: BMS, MSD, Nektar, Novartis, Pierre fabre, QBiotics; Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis, Pierre fabre, Limbic; Financial Interests, Personal, Other, Travel Support: BMS. C.U. Blank: Financial Interests, Institutional, Advisory Board: BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre; Financial Interests, Personal, Expert Testimony: Third Rock Ventures; Financial Interests, Personal, Stocks/Shares: Immagene; Financial Interests, Personal, Stocks/Shares, intention to develop IFN signature algorithm: NewCo, no name yet; Financial Interests, Institutional, Invited Speaker: BMS, Novartis, NanoString, 4SC; Other, Other, pending patent: WO 2021/177822 A1. A.M. Haydon: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD, Novartis, Pierre Fabre; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Nektar, Novartis, Pierre Fabre, Q Biotics, Roche, Limbic; Financial Interests, Personal, Other, Travel support: BMS. S. Dalle: Financial Interests, Institutional, Advisory Board: MSD, BMS; Financial Interests, Institutional, Research Grant: BMS, MSD. M.S. Carlino: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD, Novartis; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Amgen, Novartis, Pierre Fabre, Roche, IDEAYA Biosciences, Sanofi, Merck Serono, Regeneron Pharmaceuticals, QBiotics, Nektar, Eisai. A. Meshcheryakov: Financial Interests, Personal, Invited Speaker: Amgen, Bayer AG, BIOCAD, Bristol Myers Squibb, Eli Lilly, Merck, SERVIER, Takeda Pharmaceuticals, Eisai, AstraZeneca, Sanofi-Aventis; Financial Interests, Personal, Advisory Board: Amgen, Bayer AG, BIOCAD, Bristol Myers Squibb, Eli Lilly, Merck, SERVIER, Takeda Pharmaceuticals, Eisai, AstraZeneca, Sanofi-Aventis; Financial Interests, Institutional, Research Grant: Sanofi, AstraZeneca, Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel support: BIOCAD, SERVIER, Merck Sharp & Dohme, Sanofi-Aventis, Merck. S.K. Sandhu: Financial Interests, Institutional, Research Grant: Advanced Accelerators Applications (a Novartis company), Amgen, Merck Sharp & Dohme, Merck Serono, Genentech, AstraZeneca; Financial Interests, Institutional, Advisory Role: Amgen, Merck Sharp & Dohme, Merck Serono, AstraZeneca, Bristol Myer Squibb. S.S. Puig Sarda: Financial Interests, Personal, Invited Speaker: Isdin, La Roche Posay, Pfizer, Roche, Regeneron, BMS, Sunpharma; Financial Interests, Personal, Advisory Role: Isdin, Almirall, La Rohe Posay, Sanofi, Sunpharma, Pfizer, Roche, Regeneron; Financial Interests, Personal, Advisory Board: Roche, Sanofi, Sunpharma, Almirall, Isdin, Pfizer, Novartis; Financial Interests, Institutional, Research Grant: Almirall, Isdin, La Roche Posay. S. Suciu: Financial Interests, Institutional, Funding: MSD/Merck, Pierre Fabre; Financial Interests, Institutional, Research Grant: BMS. D. Grebennik: Financial Interests, Personal, Full or part-time Employment: Merck Inc., Co.. C. Krepler: Financial Interests, Personal, Full or part-time Employment: Merck Inc., Co.. P. Lorigan: Financial Interests, Personal, Advisory Role: MSD, BMS, Pierre Fabre, Novartis, Nektar, Medis Diagnostics; Financial Interests, Personal, Invited Speaker: MSD, BMS; Financial Interests, Personal, Stocks/Shares: Supportive Care; Financial Interests, Institutional, Research Grant: Pierre Fabre; Non-Financial Interests, Personal, Officer, Chair EORTC Melanoma Group: EORTC Melanoma Group; Non-Financial Interests, Personal, Officer, Past Chair Melanoma Focus Charity: Melanoma Focus Charity. C. Robert: Financial Interests, Personal, Advisory Board: BMS, Roche, Pierre Fabre, Novartis, Sanofi, MSD, AstraZeneca, Pfizer. A.M.M. Eggermont: Financial Interests, Personal, Advisory Role: Biocad, BioInvent, BioNTech, BMS, CatalYm, Ellipses, GSK, IO Biotech, ISA Pharmaceuticals, Merck/MSD, Nektar, Novartis, Pfizer, SAiRoPA, Sellas, SkylineDx, TigaTx, TTxDiscovery; Financial Interests, Personal, Invited Speaker: Biocad, BMS, Merck/MSD, Novartis; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Personal, Advisory Board: GSK, Novartis, Pfizer; Financial Interests, Personal, Stocks/Shares: SkylineDx, SAiRoPA; Non-Financial Interests, Personal, Officer: European Academy Cancer Sciences, Gerrman Cancer Aid. All other authors have declared no conflicts of interest.