Objectives: EORTC 08031 phase II trial investigated the feasibility of trimodality therapy consisting of induction chemotherapy followed by extrapleural pneumonectomy and postoperative radiotherapy in patients with cT3N1M0 or less malignant pleural mesothelioma.
Methods: Induction chemotherapy consisted of 3 courses of cisplatin 75mg/m2 and pemetrexed 500mg/m2. Non-progressing patients underwent extrapleural pneumonectomy followed by postoperative radiotherapy (54Gy, 30 fractions). Primary endpoint was “success of treatment” defined as a patient receiving the full protocol treatment, who was still alive 90 days after end of treatment without progression or grade 3-4 toxicity. A one step Fleming testing procedure was used.Secondary endpoints were toxicity, overall and progression-free survival.
Results: Fifty-nine patients were registered, 1 was ineligible. Median age was 57 years (range 26-67), cT1/T2/T3: 36/16/6, cN0/N1: 57/1. Fifty-five patients received 3 cycles of chemotherapy with only mild toxicity. Forty-six patients (79%) were operated and 42 (74%) had extrapleural pneumonectomy with a 90-day mortality of 6.5%. Postoperative radiotherapy was completed in 37 patients (65%); 2 patients (3.5%) died due to infection. Grade 3/4 toxicity persisted after 90 days in 3 patients (5.3%) due to radiation pneumonitis and bronchopleural fistula. Median overall survival time was 18.4 months (95% CI 14.8-NR) and median progression-free survival was 13.9 months (95% CI 10.9-17.1). Only 24 patients (42%) met the definition of success (one-sided 90% CI 0.36-1.00).
Conclusions: EORTC 08031 investigated the feasibility of trimodality therapy in patients with mesothelioma. Due to strictly defined timelines the primary endpoint was not met. Although overall results were similar to other series, adjustments to this trimodality therapy are necessary.