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"
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Camelia S Sima
    212 Sima
  2. Michelle S Ginsberg
    235 Ginsberg
  3. Christopher G Azzoli
    111 Azzoli
  4. Melissa Lynne Johnson
    19 Johnson
  5. Naiyer A Rizvi
    166 Rizvi
  6. Vincent Miller
    270 Miller
  7. Gregory J Riely
    600 Riely
  8. Mark Kris
    869 Kris