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 Journal Article
| Authors: | Rizvi, N. A.; Rusch, V.; Pao, W.; Chaft, J. E.; Ladanyi, M.; Miller, V. A.; Krug, L. M.; Azzoli, C. G.; Bains, M.; Downey, R.; Flores, R.; Park, B.; Singh, B.; Zakowski, M.; Heelan, R. T.; Shen, R.; Kris, M. G. |
| Article Title: | 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 |
| Abstract: | 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. ©2011 AACR. |
| Keywords: | overall survival; disease free survival; tumor regression; clinical outcome; radiographic response; molecular characteristics; cigarette smoking history |
| Journal Title: | Clinical Cancer Research |
| Volume: | 17 |
| Issue: | 10 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2011-05-15 |
| Start Page: | 3500 |
| End Page: | 3506 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-10-2102 |
| PROVIDER: | scopus |
| PUBMED: | 21558399 |
| PMCID: | PMC3261615 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 23 June 2011" - "CODEN: CCREF" - "Source: Scopus" |
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