Safety and efficacy of PD-1/PD-L1 immune checkpoint inhibitors in patients with pre-treated advanced stage malignant mesothelioma: a systematic review and meta-analysis

Background: Malignant mesothelioma is an aggressive cancer with poor prognosis. Programmed cell death protein-1 (PD-1) and its ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) have recently presented as a viable option in some first line but primarily as a second-line treatment of advanced-stage malignant mesothelioma (asMM). Therefore, this systematic review and meta-analysis aims to assess the safety and efficacy of PD-1/L-1 ICIs in advanced-stage malignant mesothelioma.

Methods: PubMed, Scopus, and Cochrane databases were searched for all studies assessing the safety and efficacy of anti PD-1/PD-L1 agents. Primary outcomes were objective response rate (ORR) and disease control rate (DCR). Secondary outcomes were median progression free (mPFS) and overall survival (mOS). Safety outcomes were treatment- (TRAEs) and immune-related adverse events (IRAEs). A random-effects meta-analysis was performed to pool medians and to derive event rates.

Results: A total of 15 studies were included with total of 1064 asMM patients. ORR and DCR were 16% and 57%, respectively. A pooled mPFS was 4.53 (CI: 3.40-5.65) and mOS was 10.51 (CI: 9.03-12.00). Overall TRAEs had an event rate of 0.69 (0.50-0.83) whereas IRAEs had an event rate of 0.28 (0.15-0.46). There were no significant differences between pembrolizumab, nivolumab primarily, and avelumab subgroups for all the outcomes. Additionally, meta-regression found no covariate to be a significant factor in ORR and DCR.

Conclusion: In this meta-analysis we found that anti-PD1/PD-L1 treatment could be useful in pretreated asMM as they had at least comparable or greater mPFS, mOS, ORR, and DCR than other second-line agents currently being used.

Registration number: This systematic review was registered at PROSPERO prior to the literature search, CRD42023442350.