Safety and tolerability of stereotactic radiotherapy combined with durvalumab with or without tremelimumab in advanced non-small cell lung cancer, the phase I SICI trial.

INTRODUCTION: This phase I study primarily addresses the safety and tolerability of Stereotactic radiotherapy on the primary tumor combined with double Immune Checkpoint Inhibition (SICI) in patients with non-small cell lung cancer (NSCLC). Increasing the release of neoantigens by radiotherapy might enhance response to immunotherapy. Especially, by targeting trunk mutations in the primary tumor. MATERIALS AND METHODS: In three sequential cohorts, immunotherapy regimes combined with stereotactic body radiotherapy (SBRT) on the primary tumor (1x20 Gy on 9 cc) were studied in stage IIIB/IV NSCLC patients progressing on chemotherapy. The first cohort (n = 3) received durvalumab. The second (n = 6) received a combination of tremelimumab and durvalumab followed by durvalumab monotherapy. The third cohort (n = 6) was similar except that the combination was reversed. Descriptive statistics were used to assess safety parameters and the exploratory outcomes of efficacy. Adverse events were reported using NCI CTCAE version 4.03. Exhaled breath was analyzed at baseline. RESULTS: Fifteen patients were included. Median irradiated volume was 9.13 cc, on a median primary tumor volume of 79 cc. There were seven patients with grade 1-2, and two patients with grade 3 treatment related adverse events. There was 1 dose limiting toxicity (colitis) with double immunotherapy. CONCLUSION: The combination of SBRT to the primary tumor and double immunotherapy in advanced NSCLC patients is safe and feasible.

Management of malignant pleural mesothelioma: have we made any progress?

As the incidence of malignant pleural mesothelioma (MPM) is increasing in the next decades, treatment is a challenge. The past 2 years have seen a number of promising achievements in the management of patients with MPM. Treatment of a symptomatic malignant pleural effusion through indwelling pleural catheter (IPC) may allow for an individualized treatment. Advances in the systemic treatment with targeted agents will undoubtedly gain by the discovery of a driver mutation which may be selectively targeted. In the meantime, the addition of monoclonal antibodies to a standard chemotherapy backbone might result in a modest improvement in outcome in patients selected for the presence of the ligand. New techniques in radiation therapy, pleural intensity-modulated radiotherapy, helical tomography and proton-therapy are exciting advances in multimodality treatment enhancing local control and therefore improving overall survival. The role of surgery remains controversial and should be further explored. Surgical procedures consist of extrapleural pneumonectomy or lung sparing operations like debulking of the parietal and visceral pleura by (extended) pleurectomy/decortication. Where the treatment in multimodality therapy may lead to improved disease-free survival and overall survival, the type of cyto-reductive procedure should be selected on institutional and surgeon's experience. The increase in mesothelioma incidence is matched only by the increasing number of researchers and studies. It is up to the clinicians to support these efforts by stimulating their patients to participate in this clinical research.