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

Abstract

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.

Keywords: NGR-hTNF; anetumab; chemotherapy; ipilimumab; malignant pleural mesothelioma (MPM); network meta-analysis; nivolumab; pembrolizumab; tremelimumab; vorinostat.

Figure 1

PRISMA flow diagram.

Figure 2

Network constructions for comparisons of overall survival (OS) and progression-free survival (PFS). (A) Network constructions for the comparison of OS (based on hazard ratios (HRs)). (B) Network constructions for the comparison in PFS (HR).

Figure 3

Summary of effect sizes based on pairwise comparisons. (A) Hazard ratios for overall survival (OS); (B) Hazard ratio for progression-free survival (PFS).

Figure 4

Cumulative ranking probability for different interventions. (A) Hazard ratio for overall survival (OS). (B) Hazard ratio for progression-free survival (PFS).