Phase II study of dasatinib in patients with advanced non-small cell lung cancer.

Abstract

7594 Background: Src-family kinases (SFK) promote cancer progression and are commonly expressed in non-small cell lung cancer (NSCLC). Preclinical data suggest that activation of epidermal growth factor receptor (EGFR) may predict response to SFK inhibition. The clinical effects of SFK inhibition in NSCLC are unknown. Methods: We completed a phase II study of the potent SFK inhibitor dasatinib as first-line therapy for advanced NSCLC. Response was measured by CT scan and metabolic activity by PET scan. Pretreatment tissue was tested for EGFR and K-Ras mutation and for phospho-SFK expression. Results: Thirty four patients with NSCLC were enrolled and treated with an initial dasatinib dose of 100 p.o. BID. An overall disease control rate of 43% was obtained. This included one durable partial response (over 2 years), four with stable disease for over 6 months, and ten additional patients with stable disease. Metabolic (PET) responses were identified in 32%. EGFR and K-Ras mutations and SFK activation in tumor did not predict response. Most patients required dose reduction. Main toxicities included fatigue and dyspnea due to underlying lung disease and pleural effusions. Pleural effusions were expected, and successfully treated with steroids, diuretics, and dose interruptions; baseline effusion predicted development of clinically significant effusion on dasatinib. Conclusions: Dasatinib has moderate clinical activity as a single agent, although lower than generally observed for chemotherapy. Marked activity in one patient and prolonged stable disease in four others indicates a subpopulation of dasatinib-sensitive patients. Supported by the NCI/CTEP, the University of Texas Lung SPORE, and Bristol-Myers Squibb. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb