• Bo Zhang, You Lang Zhou, Xinming Chen, Ziheng Wang, Qiuhong Wang, Fei Ju, Shiqi Ren, Ran Xu, Qun Xue, and Qiong Wu.
• Medical School of Nantong University, Nantong 2260, PR China; The Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong 226001, PR China.
• Int. Immunopharmacol. 2019 Mar 1; 68: 131-136.

BackgroundAlthough immune checkpoint inhibitor monotherapy has demonstrated significant efficacy in advanced melanoma, no study has systematically evaluated the efficacy and safety of the combination regimens. In this study, we conduct a comprehensive meta-analysis to explore the efficacy and safety of CTLA-4 inhibitors combined with PD-1 inhibitors or chemotherapy in advanced melanoma.MethodsWe performed a systematic search of Medline, PubMed, Embase and Web of Science for relevant clinical trials. The primary objective was to explore the efficacy and safety of combination regimens compared to monotherapy. The secondary objective was to compare the difference in efficacy between CTLA-4 inhibitors plus PD-1 inhibitors and CTLA-4 inhibitors plus chemotherapy.ResultsA total of 12 trials involving 3308 patients were included for our meta-analysis. For combination regimens compared to monotherapy, the pooled HR for overall survival (OS) was 0.67 (95%CI 0.53-0.81) and for progression-free survival (PFS) was 0.56 (95%CI 0.41-0.71). For CTLA-4 inhibitors plus PD-1 inhibitors, the combined one-year OS rate (OSR1y), six-month PFS rate (PFSR6m) and disease control rate (DCR) were 64.0% (95%CI: 49.6%-78.4%), 56.4% (95%CI: 50.1%-62.7%) and 69.9% (95%CI: 65.1%-74.7%), respectively. For CTLA-4 inhibitors plus chemotherapy, the combined OSR1y, PFSR6m and DCR were 35.2% (95%CI: 25.4%-45.0%), 54.6% (95%CI: 42.7%-66.60%) and 33.5% (95%CI: 28.0%-38.9%), respectively.ConclusionsCombination regimens significantly improved OS and PFS of advanced melanoma patients compared to monotherapy. An acceptable safety profile was observed in both CTLA-4 inhibitors plus PD-1 inhibitors and CTLA-4 inhibitors plus chemotherapy. A comparison of these two combination regimens showed that patients who received CTLA-4 inhibitors plus PD-1 inhibitors had a better therapeutic effect compared to those receiving CTLA-4 inhibitors plus chemotherapy. Further randomized clinical trials are urgently required to validate our results.Copyright © 2018 Elsevier B.V. All rights reserved.

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