A Meta-Analysis of First-Line Treatments for Unresectable Pleural Mesothelioma: Indirect Comparisons from Reconstructed Individual Patient Data of Six Randomized Controlled Trials.

Background: In unresectable pleural mesothelioma, pemetrexed+cisplatin as first line is considered the standard of care, but novel treatments have been recently proposed.

Methods: Our objective was to compare, albeit indirectly, the results of randomized controlled trials on overall survival (OS). The IPDfromKM method was employed for reconstruct individual patient data (IPD) from the graphs of Kaplan-Meier curves. Cox statistics was run to estimate hazard ratios (HRs).

Results: After a literature search on Medline (via PubMed) and Scopus databases, six randomized controlled trials were identified in which five new treatments (nivolumab plus ipilimumab, bevacizumab plus pemetrexed plus cisplatin, chemotherapy plus pembrolizumab, ONCOS-102 plus pemetrexed plus cisplatin/carboplatin and cediranib plus pemetrexed+cisplatin with maintenance with cediranib) were evaluated. In five trials, pemetrexed plus cisplatin was the standard of care given to the control arms. Nivolumab plus ipilimumab, bevacizumab plus pemetrexed plus cisplatin and chemotherapy plus pembrolizumab showed a significantly better OS compared with controls. ONCOS-102 plus pemetrexed plus cisplatin/carboplatin did not significantly improve OS. In contrast, OS worsened with cisplatin alone and with cediranib plus pemetrexed+cisplatin with maintenance with cediranib.

Discussion: Our analysis indicates that, in patients with unresectable pleural mesothelioma, three of the five novel treatments provided a significant survival benefit compared with the standard of care. Further research is needed to confirm the OS benefit found in our analysis with some treatments, whereas cisplatin alone and cediranib plus pemetrexed+cisplatin with maintenance with cediranib do not seem to deserve further research.