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

Background 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 use of platinum/pemetrexed following first-line nivolumab/ipilimumab remains scarce. Methods In this retrospective, multicenter study, 57 patients with PM who received second-line therapy were included from the MesoNet cohort, comprising twelve 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. Results 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 and median PFS with second-line platinum/pemetrexed were 11.5 months (95% 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 towards better median OS in non-epithelioid 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. Conclusion 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. MicroAbstract In pleural mesothelioma, platinum/pemetrexed offers a valid second-line treatment option with median overall survival of 11.5 months among patients initially treated with first-line nivolumab/ipilimumab, which does not appear to compromise the effect of chemotherapy.