High-dose radiotherapy adds no survival benefit after chemotherapy and radical surgery in patients with malignant pleural mesothelioma

A prospective, randomised phase II trial failed to show improvements in local relapse and overall survival when treating patient with malignant pleural mesothelioma with high-dose radiotherapy after chemotherapy and surgery. Chemotherapy followed by major surgery and irradiation of high volumes of the chest is one of the accepted treatments in very fit patients, however this combination is associated with high morbidity. These data now indicate that the irradiation has no added value and that mesothelioma patients should probably be spared the co-morbidities associated with this very intensive, combined treatment modality.

Mesothelioma remains a difficult disease to find better treatment options for. In the study at hand, researchers investigated whether high-dose hemithoracic radiotherapy would decrease the rate of, or delay the time to, local recurrence after chemotherapy and radical surgery (extrapleural pneumonectomy - EPP). The multicentre SAKK17/04 trial included 153 patients with surgically-treatable, malignant pleural mesothelioma, who were first treated with three chemotherapy cycles of cisplatin and pemetrexed, followed by surgical removal of affected lung tissue, with the goal of complete removal of the cancerous areas of lung. In the second part of the study, 54 patients were randomly assigned to receive either radiotherapy or no further treatment, with the primary endpoint being the duration of relapse-free survival (RFS).

While there had been preliminary evidence suggesting that the addition of radiotherapy might improve outcomes, the study failed to find any differences in RFS between patients treated with the additional radiotherapy and those who were not. For part 1, the median RFS was 8.8 months with a median overall survival (OS) of 15.0 months. For part 2, the median local RFS for the group who did not receive radiotherapy was 11 months (from registration) compared to 12.2 months for the irradiated patients. The OS of the patients who did not receive additional radiotherapy was 20.8 months versus 19.3 months for the irradiated patients (time from registration for both).

In summary, this study aimed for a six month delay in local recurrence, which would be meaningful for patients. However, the study results indicate that the contribution of radiation does not improve the time to recurrence of the disease. Nevertheless the investigators point out that these results should not lead to the final conclusion that there is no role for adjuvant radiation in this setting, since this study was a Phase 2 trial. New approaches (intensity modulated radiation) perhaps in future can improve the local control and reduce toxicity of the treatment, investigators commented.

Reference

Stahel R, Riesterer O, Alexandros X, et al. Neoadjuvant chemotherapy and extrapleural pneumonectomy (EPP) of malignant pleural mesothelioma (MPM) with or without hemithoracic radiotherapy: final results of the randomized multicenter phase II trial SAKK17/04. Presented at ESMO 2014; Abstract 37LBA.