A meta-analysis of randomized, controlled trials in metastatic melanoma establishes progression free survival as a surrogate for overall survival

Trial description: Background: Four randomized, phase 3 metastatic melanoma trials have shown a statistically significant overall survival (OS) benefit over the last few years. This provides the first opportunity to investigate progression free survival (PFS) as a potential surrogate for OS, taking into account a large number of recently conducted melanoma trials.Materials and Methods: A meta-analysis was performed of 10 randomized controlled trials enrolling 4,215 metastatic melanoma patients. From initially 48 published trials identified, those were selected which included DTIC as control arm, reported both PFS and OS, conform to the convention of reporting hazard ratio (HR) demonstrating benefit as <1. Experimental arm therapies included vemurafenib, dabrafenib, trametinib, sorafenib, ipilimumab, intetumumab, bosentan, oblimersen , temozolomide, and nab-paclitaxel. HRs for OS and PFS were correlated using several weighting strategies: by sample size or by precision of the HR estimate assuming fixed and random effects. Sensitivity analysis was performed including or excluding trials with crossover upon progression, phase 3 trials only, large trials, and only those with DTIC 1,000 mg/m2 dosing.