Introduction: SRC is an oncogene with an essential role in the invasiveness and metastasis of solid tumors including small cell lung cancer. 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 second-line dasatinib in patients with chemosensitive (relapse or progression ≥90 days after completing first-line therapy) small cell lung cancer. Methods: Patients with measurable disease; performance status 0 to 1; no more than one 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 two 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 April 2007 and December 2008, 45 patients were enrolled, but one patient never received any protocol therapy and one patient was ineligible: male/female, 17/26; white/black/unknown, 40/2/1; median age, 64 years (range, 35-84 years); and performance status 0/1, 12/31. No objective response was recorded among the 43 eligible and treated patients. Among the initial 27 patients, only 13 instances of PFS ≥6 weeks were observed. With a median follow-up time of 7.1 months, median estimated overall survival and PFS times for the 43 eligible and treated patients were 17.0 and 5.9 weeks, respectively. Common reasons for removal of patients from protocol treatment were progressive disease (65%) and adverse events (26%). Toxicity was generally mild to moderate: grade 3 events of >5% frequency included fatigue and pleural and pericardial effusions; and no grade 4 or 5 events were encountered. Conclusions: Dasatinib did not reach our specified efficacy criteria in this clinical setting, and the study was terminated.
Bibliographical noteFunding Information:
Supported by National Cancer Institute grants CA03927, CA33601, CA45418, CA31983, CA114558-02, and CA41287. The research for CALGB 30602 was supported, in part, by grants from the National Cancer Institute (CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chairman) and to the CALGB Statistical Center (Stephen George, PhD, CA33601). The following institutions participated in this study: Cancer Centers of the Carolinas, Greenville, SC: Jeffrey K. Giguere, MD, supported by CA29165; Christiana Care Health Services, Inc. CCOP, Wilmington, DE: Stephen Grubbs, MD, supported by CA45418; Dana-Farber Cancer Institute, Boston, MA: Harold J. Burstein, MD, supported by CA32291; Georgetown University Medical Center, Washington, DC: Edward P. Gelmann, MD, supported by CA77597; Illinois Oncology Research Association, Peoria, IL: John W. Kugler, MD, supported by CA35113; Missouri Valley Consortium-CCOP, Omaha, NE: Gamini S. Soori, MD; North Shore-Long Island Jewish Health System, New Hyde Park, NY: Daniel Budman, MD, supported by CA35279; Northern Indiana Cancer Research Consortium CCOP, South Bend, IN: Rafat Ansari, MD, supported by CA86726; Southeast Cancer Control Consortium Inc. CCOP, Goldsboro, NC: James N. Atkins, MD, supported by CA45808; The Ohio State University Medical Center, Columbus, OH: Clara D. Bloomfield, MD, supported by CA77658; University of California at San Diego, San Diego, CA: Barbara A. Parker, MD, supported by CA11789; University of Chicago, Chicago, IL: Hedy L. Kindler, MD, supported by CA41287; University of Iowa, Iowa City, IA: Daniel A. Vaena, MD, supported by CA47642; University of Maryland Greenebaum Cancer Center, Baltimore, MD: Martin Edelman, MD, supported by CA31983; University of Nebraska Medical Center, Omaha, NE: Anne Kessinger, MD, supported by CA77298; University of Vermont, Burlington, VT: Steven M. Grunberg, MD, supported by CA77406; and Wake Forest University School of Medicine, Winston-Salem, NC: David D. Hurd, MD, supported by CA03927.
- Phase II
- Small cell lung cancer