Phase II trial of dasatinib for patients with acquired resistance to treatment with the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib or gefitinib Journal Article
| Authors: | Johnson, M. L.; Riely, G. J.; Rizvi, N. A.; Azzoli, C. G.; Kris, M. G.; Sima, C. S.; Ginsberg, M. S.; Pao, W.; Miller, V. A. |
| Article Title: | Phase II trial of dasatinib for patients with acquired resistance to treatment with the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib or gefitinib |
| Abstract: | Introduction: Dual inhibition of SRC- and EGFR-dependent pathways may overcome acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for patients with lung adenocarcinoma with EGFR mutations. The SRC inhibitor dasatinib demonstrates antitumor activity in gefitinib-resistant cells lines and xenografts. Dasatinib is tolerable for patients with advanced non-small cell lung cancer, and in combination with erlotinib. Methods: We conducted this phase II study of dasatinib 70 mg twice daily in patients with EGFR-mutant lung adenocarcinoma and acquired resistance to EGFR-TKIs. After a protocol amendment based on evolving data about both drugs, patients received dasatinib at a dose of 100 mg daily with continued erlotinib after developing acquired resistance. Enrolled patients either harbored an activating mutation in EGFR or experienced clinical benefit with single-agent erlotinib or gefitinib, followed by RECIST documented progression while being treated with an EGFR-TKI. Results: Twenty-one patients were enrolled, 9 under the original trial design and 12 after the protocol amendments. We observed no complete or partial responses (0% observed rate, 95% confidence interval: 0-18%). The median time to progression was 0.5 months (range, 0.2-1.8 months) in patients treated with dasatinib and 0.9 months (range, 0.4-5 months) for patients treated with dasatinib and erlotinib in combination. Pleural effusions and dyspnea were frequent toxicities. Conclusions: Dasatinib has no activity in patients with EGFR-mutant lung adenocarcinoma with acquired resistance to erlotinib and gefitinib. Copyright © 2011 by the International Association for the Study of Lung Cancer. |
| Keywords: | lung adenocarcinoma; targeted therapies; egfr mutation; acquired resistance; src kinase |
| Journal Title: | Journal of Thoracic Oncology |
| Volume: | 6 |
| Issue: | 6 |
| ISSN: | 1556-0864 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2011-06-01 |
| Start Page: | 1128 |
| End Page: | 1131 |
| Language: | English |
| DOI: | 10.1097/JTO.0b013e3182161508 |
| PROVIDER: | scopus |
| PMCID: | PMC3230574 |
| PUBMED: | 21623279 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 23 June 2011" - "Source: Scopus" |
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