A Phase I/II Study Combining Erlotinib and Dasatinib for Non-Small Cell Lung Cancer. (28th August 2014)

• Record Type: Journal Article
• Authors: Gold, Kathryn A.; Lee, J. Jack; Harun, Nusrat; Tang, Ximing; Price, Justina; Kawedia, Jitesh D.; Tran, Hai T.; Erasmus, Jeremy J.; Blumenschein, George R.; William, William N.; Wistuba, Ignacio I.; Johnson, Faye M.
• Is Part Of: Oncologist. Volume 19:Number 10(2014)
• Page Start: 1040
• Page End: 1041
• Publication Date: 2014-08-28
• Subjects: Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2014-0228
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: Background: EGFR and Src are frequently activated in non-small cell lung cancer (NSCLC). In preclinical models, combining EGFR and Src inhibition has additive synergistic effects. We conducted a phase I/II trial of the combination of Src inhibitor dasatinib with EGFR inhibitor erlotinib to determine the maximum tolerated dose (MTD), pharmacokinetic drug interactions, biomarkers, and efficacy in NSCLC. Methods: The phase I 3+3 dose-escalation study enrolled patients with solid tumors to determine the MTD. The phase II trial enrolled patients with advanced NSCLC who had undergone no previous treatments to determine progression-free survival (PFS) and response. Pharmacokinetic and tissue biomarker analyses were performed. Results: MTD was 150 mg of erlotinib and 70 mg of dasatinib daily based on 12 patients treated in the phase I portion. No responses were observed in phase I. The 35 NSCLC patients treated in phase II had an overall disease control rate of 59% at 6 weeks. Five patients (15%) had partial responses; all had activating EGFR mutations. Median PFS was 3.3 months. Epithelial-mesenchymal transition markers did not correlate with outcomes. Conclusion: The combination of erlotinib and dasatinib is safe and feasible in NSCLC. The results of this study do not support use of this combination in molecularly unselected NSCLC.