Salvage Therapy for Relapsed Malignant Pleural Mesothelioma: A Systematic Review and Network Meta-Analysis

Simple Summary Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited therapeutic options. Pemetrexed plus platinum is a standard first-line therapy, but options for second-line therapy in patients with relapsed mesothelioma remain controversial. Several drugs were recently introduced to treat relapsed MPM. We conducted a comprehensive systematic review and network meta-analysis to evaluate the efficacy of these drugs according to published randomized controlled trials. Nivolumab alone or nivolumab plus ipilimumab provided significantly longer overall survival (OS), and treatment with nivolumab plus ipilimumab was associated with the best OS based on the surface under the cumulative ranking curve (SUCRA). The network meta-analysis revealed that tremelimumab, vorinostat, chemotherapy (CTX), asparagine-glycine-arginine-human tumor necrosis factor plus CTX, nivolumab alone, and nivolumab plus ipilimumab all produced significant progression-free survival (PFS) benefits compared with placebo, with nivolumab plus ipilimumab ranked first for PFS according to SUCRA. Patients with malignant pleural mesothelioma (MPM) have very poor prognoses, and pemetrexed plus platinum is the standard first-line therapy. However, the second-line therapy for relapsed MPM remains controversial. A comprehensive search was performed to identify randomized controlled trials (RCTs) evaluating various second-line regimens in patients with relapsed MPM. Indirect comparisons of overall survival (OS) and progression-free survival (PFS) were performed using network meta-analysis. Surface under the cumulative ranking curve (SUCRA) values were used to rank the included treatments according to each outcome. Nivolumab alone or nivolumab plus ipilimumab provided significantly longer OS than placebo (hazard ratio (HR): 0.72, 95% confidence interval (CI): 0.55-0.94 for nivolumab alone; HR: 0.54, 95% CI: 0.31-0.92 for nivolumab plus ipilimumab). The best SUCRA ranking for OS was identified for nivolumab plus ipilimumab (SUCRA: 90.8%). Tremelimumab, vorinostat, nivolumab alone, chemotherapy (CTX), asparagine-glycine-arginine-human tumor necrosis factor plus CTX, and nivolumab plus ipilimumab all produced noticeable PFS benefits compared with placebo. Nivolumab plus ipilimumab had the best PFS ranking (SUCRA: 92.3%). Second-line treatment with nivolumab plus ipilimumab provided the OS and PFS outcomes for patients with relapsed MPM.