A Randomised Phase II Study of Extended Pleurectomy/decortication Preceded or Followed by Chemotherapy in Patients with Early-Stage Pleural Mesothelioma: EORTC 1205.

Background The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication. The most optimal sequence of surgery and chemotherapy remains unknown. Methods EORTC-1205-LCG was a multicentric, noncomparative phase 2 trial, 1:1 randomising between immediate (arm A) and deferred surgery (arm B), followed or preceded by chemotherapy. Eligible patients (Eastern Cooperative Oncology Group 0 - 1) had treatment-na & iuml;ve, borderline resectable T1 - 3 N0 - 1 M0 mesothelioma of any histology. Primary outcome was rate of success at 20 weeks, a composite end-point including 1) successfully completing both treatments within 20 weeks; 2) being alive with no signs of progressive disease; and 3) no residual grade 3 - 4 toxicity. Secondary end-points were toxicity, overall survival, progression-free survival and process indicators of surgical quality. Findings 69 patients were included in this trial. 56 (81%) patients completed three cycles of chemotherapy and 58 (84%) patients underwent surgery. Of the 64 patients in the primary analysis, 21 out of 30 patients in arm A (70.0%; 80% CI 56.8 - 81.0%) and 17 out of 34 patients (50.0%; 80% CI 37.8 - 62.2%) in arm B reached the statistical end-point for rate of success. Median progression-free survival and overall survival were 10.8 (95% CI 8.5 - 17.2) months and 27.1 (95% CI 22.6 - 64.3) months in arm A, and 8.0 (95% CI 7.2 - 21.9) months and 33.8 (95% CI 23.8 - 44.6) months in arm B. Macroscopic complete resection was obtained in 82.8% of patients. 30- and 90-day mortality were both 1.7%. No new safety signals were found, but treatment-related morbidity was high. Interpretation EORTC 1205 did not succeed in selecting a preferred sequence of pre- or post-operative chemotherapy. Either procedure is feasible with a low mortality, albeit consistent morbidity. A shared informed decision between surgeon and patient remains essential.