Benefit with first-line ICIs in mesothelioma

Abstract

0123456789();: Nature reviews | CliniCal OnCOlOgy The combination of platinum agents with pemetrexed has been the standardofcare treatment for unresectable malignant pleural mesothelioma (MPM), although outcomes remain poor. Now, the results of CheckMate 743 show that these patients can derive an overall survival (OS) benefit from immunecheckpoint inhibitors (ICIs). In this phase III trial, 605 patients were randomly assigned (1:1) to receive nivolumab plus ipilimumab or standard chemotherapy. Median OS (mOS) durations were longer with the ICIs: 18.1 months versus 14.1 months with chemotherapy (HR 0.74, 96.6% CI 0.60–0.91; P = 0.002). With the exception of patients aged ≥75 years (HR 1.02, 96.6% CI 0.70–1.48), this OS benefit was observed across all subgroups. In patients with nonepithelioid MPM, mOS was 18.1 months versus 8.8 months (HR 0.46, 95% CI 0.31–0.68) and in those with epithelioid MPM, it was 18.7 months versus 16.5 months (HR 0.86, 95% CI 0.69–1.08). Of note, mOS was similar in patients receiving ICIs regardless of PDL1 status: 18.0 months versus 17.3 months for PDL1 tumour expression levels ≥1% and <1%, respectively. Numerical differences in median progressionfree survival durations were not significant: 6.8 months and 7.2 months with ICIs and chemotherapy, respectively (HR 1.00, 95% CI 0.82–1.21). Objective response rates were also similar (40% versus 43%), although only patients receiving ICIs had complete responses (2%). The incidence of grade 3–4 treatmentrelated adverse events was 30% and 32% with ICIs and chemotherapy, respectively, and 3 versus 1 treatmentrelated deaths occurred. In October 2020, the FDA approved nivolumab plus ipilimumab for the firstline treatment of patients with unresectable MPM based on these results. This regimen should be considered a new standard of care for these patients. Studies to identify predictive biomarkers, in particular in those with epithelioid MPM, are warranted.