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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MSK Authors
  1. Valerie W Rusch
    652 Rusch
  2. Lee M Krug
    211 Krug
  3. Bhuvanesh Singh
    206 Singh
  4. Christopher G Azzoli
    105 Azzoli
  5. Ronglai Shen
    127 Shen
  6. William Pao
    141 Pao
  7. Naiyer A Rizvi
    156 Rizvi
  8. Vincent Miller
    261 Miller
  9. Marc Ladanyi
    864 Ladanyi
  10. Jamie Erin Chaft
    126 Chaft
  11. Raja Flores
    107 Flores
  12. Maureen F Zakowski
    275 Zakowski
  13. Bernard J Park
    155 Park
  14. Robert J Downey
    202 Downey
  15. Manjit S Bains
    227 Bains
  16. Mark Kris
    597 Kris
  17. Robert T Heelan
    79 Heelan