Real-world overall survival with platinum–pemetrexed chemotherapy versus ipilimumab–nivolumab in peritoneal mesothelioma: A propensity-matched multicenter analysis.

Abstract

e23442 Background: Peritoneal mesothelioma is a rare malignancy with limited data guiding optimal first-line systemic therapy. Platinum–pemetrexed has historically been the standard regimen. Dual immune checkpoint inhibition with ipilimumab plus nivolumab is now guideline-recommended, largely based on pleural mesothelioma data. Comparative real-world effectiveness data in peritoneal mesothelioma are limited. We compared outcomes between these two first-line strategies. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, identifying adults with peritoneal mesothelioma who received first-line platinum–pemetrexed or ipilimumab plus nivolumab. The index date was treatment initiation. Baseline characteristics were assessed. One-to-one propensity score matching was performed using demographics and major comorbidities. Overall survival (OS) was evaluated using Kaplan–Meier methods with log-rank testing over the full follow-up period and at fixed time points (6 months, 1 year, and 3 years). Results: Before matching, 389 patients received platinum–pemetrexed and 108 received ipilimumab–nivolumab. The immunotherapy cohort had a higher burden of comorbidities, including heart failure and chronic kidney disease. After matching, 88 patients per cohort were included with balanced baseline characteristics. No significant difference in OS was observed. Death occurred in 48/88 (54.5%) in the chemotherapy cohort and 42/88 (47.7%) in the immunotherapy cohort (risk ratio 1.14, 95% CI 0.86–1.53; log-rank p = 0.36). Median OS was 609 days with chemotherapy and 426 days with immunotherapy. Survival probabilities at the end of follow-up were 28.4% and 17.6%, respectively. At 6 months, OS was 72.6% with chemotherapy and 66.3% with immunotherapy (p = 0.42). At 1 year, OS was 54.4% versus 56.5% (p = 0.94). At 3 years, OS was 34.4% versus 37.7% (p = 0.94). No time point demonstrated a statistically significant survival difference between the two cohorts. Conclusions: In this real-world multicenter analysis, ipilimumab plus nivolumab did not demonstrate a significant overall survival advantage compared with platinum–pemetrexed after propensity score matching. Outcomes were comparable across early and long-term time points. Prospective, peritoneal mesothelioma–specific trials are needed to define optimal first-line therapy. Overall survival comparison after propensity score matching. Time Point Chemotherapy OS (%) ICI OS (%) Risk ratio (95% CI) Log-rank p 6 months 72.6 66.3 0.89 (0.55-1.42) 0.42 1 year 54.4 56.5 1.16 (0.80-1.69) 0.94 3 years 34.4 37.7 1.26 (0.93-1.71) 0.94 Overall follow-up 28.4 17.6 1.14 (0.86- 1.53) 0.36