Brief Report: A Phase II Study of Sunitinib in Malignant Pleural Mesothelioma. The NCIC Clinical Trials Group

Introduction: Malignant pleural mesothelioma (MPM) is an aggressive malignancy that most often presents at an advanced, incurable stage. After the failure of standard first-line cisplatin/antifolate chemotherapy, there is no accepted treatment. The vascular endothelial growth factor pathway may be a relevant therapeutic target in MPM. Methods: This open-labeled phase II trial evaluated single-agent sunitinib, an inhibitor of multiple receptor tyrosine kinases including the vascular endothelial growth factor receptors, given at 50 mg daily orally for 4 weeks followed by a 2-week rest, in patients with advanced MPM. Two cohorts were studied: cohort 1, in which patients had previously received cisplatin-based chemotherapy, and cohort 2, consisting of previously untreated patients. A two-stage design was used for both cohorts; the primary outcome was objective response rate as determined by the RECIST criteria modified for MPM. Secondary outcomes included rates and duration of disease control, progression-free survival and overall survival, and safety and tolerability. Results: A total of 35 eligible patients were enrolled (17 to cohort 1 and 18 to cohort 2). Neither cohort met the criteria for continuing to the second stage of accrual; only one objective response, confirmed by independent review, was observed in a previously untreated patient. Median progression-free and overall survivals were 2.8 and 8.3 months in cohort 1, and 2.7 and 6.7 months in cohort 2, respectively. Observed toxicity was within that expected for sunitinib. Conclusions: Sunitinib, similar to other angiogenesis inhibitors, has limited activity in MPM. Future trials of angiogenesis inhibitors given as single agents in unselected patients with MPM are not warranted.