Maintenance pemetrexed after platinum pemetrexed chemotherapy and survival outcomes in malignant pleural mesothelioma in a multicenter real world study

Abstract

Abstract Malignant pleural mesothelioma (MPM) is an aggressive malignancy with poor prognosis, and the role of maintenance therapy after first-line platinum–pemetrexed chemotherapy remains unclear. We conducted a multicenter retrospective study including 96 patients with metastatic or unresectable MPM treated across eight tertiary oncology centers. Eligible patients had received at least four cycles of first-line platinum–pemetrexed and achieved disease control, after which they were either administered maintenance pemetrexed ( n  = 54) or observed without further treatment ( n  = 42). Maintenance pemetrexed was associated with significantly prolonged median progression-free survival (15.5 vs. 7.9 months; p  < 0.001) and overall survival (22.3 vs. 16.4 months; p  = 0.002) compared with observation. Multivariate analyses confirmed maintenance pemetrexed as an independent predictor of improved progression-free survival (HR 2.92; 95% CI 1.81–4.72; p  < 0.001) and overall survival (HR 2.10; 95% CI 1.24–3.55; p  = 0.005). Non-epithelioid histology was independently associated with worse outcomes. Subgroup analyses demonstrated that the survival benefit of maintenance pemetrexed persisted in patients achieving both partial response and stable disease after first-line chemotherapy. Importantly, maintenance therapy was well tolerated, with no discontinuations due to toxicity, highlighting its feasibility in routine practice. These real-world findings suggest that maintenance pemetrexed may be associated with improved survival outcomes in patients with MPM who achieve disease control after first-line therapy.