Efficacy and safety profile of combining antiangiogenic agents with chemotherapy in patients with advanced malignant pleural mesothelioma: A systematic review and meta-analysis of randomized controlled trials

Objectives: Several prospective trials had been reported on chemotherapy with or without antiangiogenic agents in patients with advanced malignant pleural mesothelioma (MPM), with diverse results. We performed this systematic review and meta-analysis to evaluate the efficacy and safety of the combination regimen.

Methods: We systematically identified trials in several databases, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ASCO Abstracts and ESMO Abstracts. All the randomized controlled trials (RCTs) about chemotherapy combined with antiangiogenic agents in advanced MPM were identified. Overall survival (OS) was the primary outcome, while progression-free survival (PFS), overall response rate (ORR) and serious toxicities were the secondary outcomes. Review Manager 5.3 was used to perform the statistical analyses. Stata 12.0 was used to assess the publication bias of egger's test.

Results: 5 randomized controlled trials containing 1250 patients were finally included in this analysis. Statistical analyses showed that the addition of antiangiogenic agents to chemotherapy could prolong OS [HR 0.79 (0.71-0.89), p<0.0001] and PFS [HR 0.75 (0.68-0.84), p<0.00001] in advanced MPM, especially in the epithelioid subgroup, with a tolerable toxicity profile. No significant difference was found in the analysis of ORR [HR 1.13 (0.95-1.35), p = 0.18]. Heterogeneity was found in the analyses of PFS and ORR, which might be caused by the limitation in uniform evaluation of tumor response.

Conclusions: The combination of antiangiogenic agents with chemotherapy showed superior over chemotherapy alone in patients with advanced MPM. More prospective trials should be warranted to identify patients who would most likely benefit from the combination regimen.