LBA37_PR - Neoadjuvant chemotherapy and extrapleural pneumonectomy (EPP) of malignant pleural mesothelioma (MPM) with or without hemithoracic radiotherapy: Fi...

Date 29 September 2014
Event ESMO 2014
Session SCLC and other thoracic malignancies
Topics Anti-Cancer Agents & Biologic Therapy
Mesothelioma
Surgery and/or Radiotherapy of Cancer
Presenter Rolf Stahel
Citation Annals of Oncology (2014) 25 (5): 1-41. 10.1093/annonc/mdu438
Authors R.A. Stahel1, O. Riesterer2, X. Alexandros3, I. Opitz4, M. Beyeler5, A. Ochsenbein6, M. Früh7, R. Cathomas8, K. Nackaerts9, S. Peters10, C. Mamot11, A. Zippelius12, C. Mordasini13, K. Clemens14, K. Eckhardt15, R. Schmid16, W. Nagel17, D. Aebersold18, O. Gautschi19, W. Weder20
  • 1Clinik Of Oncology, Universitätsspital Zürich, 8091 - Zürich/CH
  • 2Radio-onkologie, Universitätsspital Zürich, 8091 - Zürich/CH
  • 3Biostatistics, SAKK Cordination Center, Bern/CH
  • 4Thoracic Surgery, University Hospital Zurich, Zurich/CH
  • 5Sakk Coordination Center, SAKK Coordination Center, Bern/CH
  • 6Medical Oncology, Inselspital Bern, Bern/CH
  • 7Medical Oncology, Kantonsspital St. Gallen, St. Gallen/CH
  • 8Medizinische Onkologie, Kantonsspital Graubünden, 7000 - Chur/CH
  • 9Respiratory Oncology Unit, Univ Hospital Leuven, 3000 - Leuven/BE
  • 10Oncology, Centre Hospitalier Universitaire Vaudois - CHUV, 1011 - Lausanne/CH
  • 11Medical Oncology, Kantonsspital Aarau, Aarau/CH
  • 12Medical Oncology, University Hospital Basel, 4031 - Basel/CH
  • 13Onkologie, Tifenau Spital, Bern/CH
  • 14Onkologie, Kantonsspital Baden, Baden/CH
  • 15Sakk Coordinating Center, SAKK Coordinating Center, Bern/CH
  • 16Thoracic Surgery, Inselspital Bern, Bern/CH
  • 17Klinik Für Chirurgie, Kantonsspital St. Gallen, St. Gallen/CH
  • 18Radio-onkologie, Inselspital Bern, Bern/CH
  • 19Klinik Für Onkologie, Luzerner Kantonsspital, 6000 - Luzern/CH
  • 20Division Of Thoracic Surgery, Universitätsspital Zürich, 8091 - Zürich/CH

 

Abstract

Aim

We have previously documented the feasibility of neoadjuvant chemotherapy and EPP in a multicenter trial of MPM (Weder, Ann Oncol 18: 1196, 2007). The objectives of the trimodality trial SAKK17/04 (NCT00334594) were to evaluate the time to loco-regional relapse with or without high dose hemithoracic radiotherapy in a prospective multicenter randomized phase II trial in patients with R0 and R1 resection after neoadjuvant chemotherapy and EPP.

Methods

Eligible patients had pathologically confirmed MPM, surgically resectable TNM stage (T1-3 N0-2 M0), PS0-1, ages 18-70 years. Part 1 had a phase II design, and included neoadjuvant chemotherapy with 3 cycles of cisplatin and pemetrexed, followed by restaging and EPP. The primary endpoint of part 1 was complete macroscopic resection (R0-1). Part 2 randomized consenting patients with R0-1 resection into two parallel phase II arms (control arm A and radiotherapy arm B). The primary endpoint for part 2 was loco-regional relapse-free survival (RFS). To detect a 1 year increase with 80% power and 10% alpha, 37 patients were needed for arm B. Secondary endpoints included operability, tolerability of chemotherapy and radiotherapy, survival, and translational research

Results

Because accrual of part 2 was slower than planned, the trial was stopped in 2013. Overall, 153 patients entered the trial, of whom 125 underwent surgery and 99 had a complete macroscopic resection (primary endpoint part 1). Of the later patients, 54 could be randomized 1:1 into each arm. Reasons for non-randomization included patient refusal in 24 and ineligibility or protocol deviations in 21. Of the 27 patients randomized to hemithoracic radiotherapy, 25 completed the treatment as planned. For part 1 the median RFS was 8.8 (95%CI: 7.3–10.7) and median OS was 15.0 (95% CI: 12.1–19.3) months. For part 2 the median local RFS for group A was 7.6 (95%CI: 5.5–10.7) and for group B 9.4 (95%CI: 6.5-11.9) months (primary endpoint part 2), while the overall RFS and OS for group A were 5.7 (95%CI: 3.5-8.8) and 16.9 (95%CI: 10.7-23.6) months and for group B 7.6 (95% CI:5.2-10.6) and 14.9 (95%CI: 7.0–17.6) months.

Conclusions

This study did not reach the primary endpoint which was defined as one-year increase in loco-regional relapse-free survival and thus does not support the routine use of hemithoracic RT after neoadjuvant chemotherapy and EPP.

Disclosure

All authors have declared no conflicts of interest.