Evaluating the potential of relapse-free survival as a surrogate for overall survival in the adjuvant therapy of melanoma with checkpoint inhibitors.

Introduction: Recent changes in the adjuvant treatment of melanoma have raised interest in confirming relapse-free survival (RFS) as a surrogate for overall survival (OS).
Methods: We explore this issue with the meta-analytic framework, using individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 18071 trial of ipilimumab and published results from other adjuvant trials.
Results: The individual patient data analysis results at a median follow-up of 5.3 years showed a strong association between RFS and OS at the patient level (ρ = 0.84; 95% confidence interval [CI]: 0.82-0.87) and a moderate association at the trial level (R ²  = 0.59; 95% CI: 0.08-1.00).
Conclusions: The trial-level association previously observed in interferon-based trials appeared to be maintained when the EORTC 18071 results were added to a regression analysis using published results from other trials. More data from adjuvant trials are required to confirm the strength of association between RFS and OS in this setting.
Competing Interests: Conflict of interest statement M.B. reports receiving personal fees and other from funds from IDDI, outside of the submitted work. G.de.S. and S.S. report receiving Bristol-Myers Squibb Grant to the EORTC HQ. A.E.reports receiving personal fees from Biocad, BioInvent, BMS, Ellipses, GSK, ISA Pharmaceuticals, IO Bioteck, Merk&Co/MSD, Nektar, Novartis, Sanofi, Sellas and SkylineDx; personal fees from Biocad, MSD, Novartis, GSK, Novartis and Pfizer and other fees from BMS, outside the submitted work. A.M. and S.K. are employees of and hold stock/stock options in Bristol Myers Squibb. E.C, E.D.S. and P.S. report receiving employer IDDI and consultancy fees from BMS during the conduct of the study. J.S.W. reports receiving grants from BMS, Merck and Novartis, outside the submitted work; In addition, J.S.W. has been named on a PD-1 biomarker patent by Biodesix and on a CTLA4 biomarker patent by Moffitt Cancer Center.
(Copyright © 2020. Published by Elsevier Ltd.)