Pembrolizumab plus Chemotherapy for Pleural Mesothelioma

First-line immunotherapy with ipilimumab and nivolumab is the first new standard of care for mesothelioma since the introduction of pemetrexed in 2004. However, not all patients benefit, and there is interest in development of chemoimmunotherapy regimens. In an international, open-label, randomized, phase 3 trial, researchers evaluated platinum plus pemetrexed chemotherapy with or without pembrolizumab in 440 patients with untreated, unresectable, advanced pleural mesothelioma. Patients were stratified by histologic subtype before randomization; chemotherapy was given for up to 6 cycles, pembrolizumab for up to 2 years.

At a median follow-up of 16.2 months, overall survival (OS) was longer with pembrolizumab than with chemotherapy alone (median, 17.3 vs. 16.1 months; hazard ratio, 0.79). Exploratory analysis showed that the OS benefit with pembrolizumab was maintained regardless of PD-L1 expression, and the magnitude of benefit was greater in patients with the nonepithelioid subtype. The addition of pembrolizumab also improved the objective response rate (62% vs. 38%; P<0.0001; odds ratio, 2.7). Grade 3 or 4 treatment-emergent adverse events occurred in 27% of patients receiving pembrolizumab and 15% receiving chemotherapy alone.