Clinical and Molecular Characteristics Associated with Survival in Advanced Melanoma Treated with Checkpoint Inhibitors

Abstract

Background. We performed meta-analysis to gather more evidence regarding clinical-molecular subgroups associated with better overall survival (OS) in advanced melanoma treated with checkpoint inhibitors. Materials and Methods. We performed a systematic search of PubMed, Scopus, Cochrane Library, and clinical trial.gov. Randomized clinical trials that compared a checkpoint inhibitor (nivolumab or pembrolizumab) with investigator choice chemotherapy or ipilimumab were included in our study. Hazard ratios (HR) and confidence interval (CI) were calculated for progression-free survival (PFS) and OS for each subgroup using generic inverse model along with the random effect method. Results. A total of 6 clinical trials were eligible for the meta-analysis. OS was prolonged in wild BRAF subgroup (HR 0.65, 95% CI 0.49-0.85, p 0.002), Programmed cell death subgroup (PD-1+) (HR 0.57, 95% CI 0.41-0.80, p 0.001), and high lactate dehydrogenase (LDH) level subgroup (HR 0.60, 95% CI 0.38-0.95, p 0.03). Similarly, we found increased OS in eastern cooperative oncology group (ECOG) 1, males and age >65 years subgroups. Conclusions. Checkpoint inhibitors significantly increased OS in patients with wild BRAF, positive PD-1, and high LDH. However, results should be interpreted keeping in mind associated significant heterogeneity. The results of this study should help in designing future clinical trials.