A Phase II study of dasatinib in patients with chemo-sensitive relapsed small cell lung cancer (SCLC): CALGB 30602

Abstract

BACKGROUND: SRC is an oncogene with an essential role in the invasiveness and metastasis of solid tumors including SCLC. Dasatinib is a potent inhibitor of SRC as well as other tyrosine kinases. The primary objective of this study was to determine the efficacy of secondline dasatinib in patients with chemo-sensitive (relapse or progression ≥90 days after completing first-line therapy) SCLC. METHODS: Patients with measurable disease, performance status (PS) 0-1, no more than 1 prior platinum-based chemotherapy regimen, and adequate hematologic, hepatic, and renal function were eligible. Dasatinib was administered orally at 70 mg twice daily continuously (1 cycle = 21 days) until disease progression or unacceptable toxicity. Response was determined after every 2 cycles. Patients were followed until disease progression or death. The study was prospectively designed to simultaneously discriminate between complete plus partial response rates of 5% versus 20% and progression-free survival (PFS) rates at 6 weeks of 50% versus 70.7% in 53 evaluable patients with at least 92% power. The study was to be terminated early and declared negative if 1 or less objective response and 14 or fewer instances of PFS ≥ 6 weeks were observed among the initial 27 patients; however, patient accrual continued while the initial 27 patients were evaluated. RESULTS: Between 4/2007 and 12/2008, 45 patients were enrolled: male/female, 17/28; white/black/other, 42/2/1; median age, 69 (range, 36-88) years; and PS 0/1, 12/33. No objective response was recorded among all 45 patients. Among the initial 27 patients, only 13 instances of PFS ≥ 6 weeks were observed. With a median follow up time of 1.6 months, the median estimated overall survival and PFS times for all 45 patients were 22 and 6 weeks, respectively. Common reasons for removal of patients from protocol treatment were progressive disease (51%) and adverse events (27%). Toxicity was generally mild to moderate: grade 3 events of approximately 10% frequency included fatigue, pleural and pericardial effusions, and dyspnea, but higher grade toxicity was infrequent. CONCLUSIONS: Dasatinib did not reach our specified efficacy criteria in this clinical setting, and the study was terminated.