Outcomes of Platinum Plus Pemetrexed and Treatment Patterns Following First-Line Nivolumab and Ipilimumab in Pleural Mesothelioma: Real-World Results From the German MesoNet Study.

There is currently no approval for second-line treatment in pleural mesothelioma (PM). Since the approval of nivolumab/ipilimumab, most guidelines recommend platinum/pemetrexed as subsequent treatment. However, the data supporting this sequence are primarily based on efficacy observed in the first-line setting, while evidence regarding the use of platinum/pemetrexed following first-line nivolumab/ipilimumab remains scarce. In this retrospective, multicenter study, 57 patients with PM who received second-line therapy were included from the MesoNet cohort, comprising 12 participating cancer centers across Germany. The primary objective was to evaluate outcomes in patients who received second-line platinum/pemetrexed following nivolumab/ipilimumab. The secondary objective was to explore subsequent treatment patterns. Among 135 patients treated with first-line nivolumab/ipilimumab, 57 (42%) received second-line treatment, of whom 41 (72%) received platinum/pemetrexed. The median OS (overall survival) and median PFS (progression-free survival) with second-line platinum/pemetrexed were 11.5 months (95% confidence intervals [CI] 8.6-13.8) and 5.8 months (95% CI 4.1-7), respectively. The disease control rate was 72%, with partial response observed in 28% of patients. Subtype analysis revealed a trend toward better median OS in nonepithelioid versus epithelioid histology (13 months vs. 9.5 months). Only 22 patients (16% of the first-line cohort) received third-line treatment, indicating substantial treatment attrition. In this real-world study, second-line platinum/pemetrexed following first-line nivolumab/ipilimumab demonstrated meaningful clinical activity with an mOS of 11.5 months from the initiation of second-line treatment. These findings support platinum/pemetrexed as an effective second-line option in this setting. However, the high treatment attrition rate emphasizes the importance of careful patient selection and early initiation of second-line therapy.