Background
Phase 2 multicenter feasibility trial (EORTC 08031). N=58 evaluable, malignant pleural mesothelioma (MPM) ≤cT3N1M0. Trimodality therapy (induction chemo → EPP → postoperative RT); primary goal feasibility within protocol-defined timelines.
Interventions and follow up
Treatment: Induction cisplatin 75 mg/m² + pemetrexed 500 mg/m² × 3 cycles; non-progressors → extrapleural pneumonectomy (EPP) → postoperative hemithoracic RT
Primary endpoint: Feasibility ("success" = trimodality completed within protocol timelines)
mFollow up: NR
Primary endpoint: Feasibility ("success" = trimodality completed within protocol timelines)
mFollow up: NR
Results
Induction completion: 93% (55/59 evaluable) completed 3 chemotherapy cycles
EPP rate: 79% (46/58) surgery; 74% (42/58) EPP; 90-day post-EPP mortality 6.5%
RT completion: 65% (37/57) completed postoperative RT
"Success" rate: 42% (24/57) (one-sided 90% CI 0.36–1.00)
Median OS: 18.4 months (95% CI 15.6–32.9)
Median PFS: 13.9 months
EPP rate: 79% (46/58) surgery; 74% (42/58) EPP; 90-day post-EPP mortality 6.5%
RT completion: 65% (37/57) completed postoperative RT
"Success" rate: 42% (24/57) (one-sided 90% CI 0.36–1.00)
Median OS: 18.4 months (95% CI 15.6–32.9)
Median PFS: 13.9 months
Adverse events
Induction: Grade 3–4 in minority
EPP 90-day mortality: 6.5%
Postoperative RT grade 3–4 persistent toxicity: 5.3% (3 patients) beyond 90 days
Other: No unexpected toxicities from the combined approach
EPP 90-day mortality: 6.5%
Postoperative RT grade 3–4 persistent toxicity: 5.3% (3 patients) beyond 90 days
Other: No unexpected toxicities from the combined approach
Conclusions
Trimodality therapy for MPM was feasible but completed within strict protocol timelines in only 42%. Median OS 18.4 months is consistent with other selected trimodality series.
Key Limitations
Single-arm feasibility design, no comparator; small N; tight protocol timelines drove low "success" rate; highly selected resectable patients limit generalizability.
Clinical Context
EPP-based trimodality has since fallen out of favor (MARS series); lung-sparing P/D with hemithoracic IMRT (IMPRINT) and systemic-therapy-forward approaches are now preferred for MPM.