Molecular Characteristics Predict Clinical Outcomes: Prospective Trial Correlating Response to the EGFR Tyrosine Kinase Inhibitor Gefitinib with the Presence of Sensitizing Mutations in the Tyrosine Binding Domain of the EGFR Gene
| Autor: | Marc Ladanyi, Ronglai Shen, Maureen F. Zakowski, Naiyer A. Rizvi, Bernard J. Park, Mark G. Kris, Jamie E. Chaft, Robert T. Heelan, Christopher G. Azzoli, Raja M. Flores, William Pao, Bhuvanesh Singh, Manjit S. Bains, Vincent A. Miller, Valerie W. Rusch, Lee M. Krug, Robert J. Downey |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Cancer Research Lung Neoplasms medicine.drug_class medicine.disease_cause Article Tyrosine-kinase inhibitor Gefitinib Carcinoma Non-Small-Cell Lung Catalytic Domain medicine Carcinoma Humans Epidermal growth factor receptor Protein Kinase Inhibitors Survival analysis Aged Aged 80 and over Tyrosine binding biology business.industry Cancer Genes erbB-1 Middle Aged Prognosis medicine.disease Survival Analysis respiratory tract diseases ErbB Receptors Treatment Outcome Oncology Drug Resistance Neoplasm Mutation Quinazolines Cancer research biology.protein Tyrosine Female KRAS business Protein Binding medicine.drug |
| Zdroj: | Clinical Cancer Research. 17:3500-3506 |
| ISSN: | 1557-3265 1078-0432 |
| Popis: | Purpose: To determine if tumor regression following treatment with gefitinib correlates with the presence of sensitizing mutations in epidermal growth factor receptor (EGFR). Patients and Methods: Patients with resectable stage I and II non–small cell lung cancer (NSCLC) enriched for the likelihood of EGFR mutation (≤15 pack-year cigarette smoking history and/or a component of bronchioloalveolar carcinoma) received preoperative gefitinib for 21 days. Tumor specimens were analyzed for EGFR and KRAS mutations and EGFR protein expression and amplification. Patients with 25% or more reduction in tumor size measured bidimensionally at 3 weeks and/or patients with an EGFR mutation received adjuvant gefitinib for 2 years postoperatively. Results: Fifty patients with stage I/II NSCLC were treated. After 21 days of preoperative gefitinib a response of 25% or more was observed in 21 of 50 (42%) patients. Seventeen of 21 patients with a response had an EGFR mutation and 4 of 21 patients with a response did not (P = 0.0001). Twenty-five of 50 patients were eligible to receive adjuvant gefitinib. With a median follow-up of 44.1 months, 2-year disease free survival for EGFR mutant patients and for those who received adjuvant gefitinib was not statistically different than those who were EGFR wild-type and those who did not receive adjuvant gefitinib. The median disease free and overall survivals have not been reached. Conclusions: The presence of sensitizing EGFR mutations correlates with radiographic response. A short course of preoperative treatment serves a platform for evaluating activity of new agents and assures sufficient tumor availability for correlative analyses. Clin Cancer Res; 17(10); 3500–6. ©2011 AACR. |
| Databáze: | OpenAIRE |
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