Phase II Trial of Dasatinib for Patients with Acquired Resistance to Treatment with the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Erlotinib or Gefitinib

Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer (Impact Factor: 5.8). 06/2011; 6(6):1128-31. DOI: 10.1097/JTO.0b013e3182161508
Source: PubMed

ABSTRACT 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.
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.
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.
Dasatinib has no activity in patients with EGFR-mutant lung adenocarcinoma with acquired resistance to erlotinib and gefitinib.

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