Increased Epidermal Growth Factor Receptor Gene Copy Number Detected by Fluorescence In Situ Hybridization Associates With Increased Sensitivity to Gefitinib in Patients With Bronchioloalveolar Carcinoma Subtypes: A Southwest Oncology Group Study

DOI Web Site 被引用文献19件
  • Fred R. Hirsch
    From the University of Colorado Health Sciences Center, Denver, CO; Southwest Oncology Group Statistical Center, San Antonio, TX; Puget Sound Oncology Consortium, Seattle, WA; and University of California, Davis Cancer Center, Sacramento, CA
  • Marileila Varella-Garcia
    From the University of Colorado Health Sciences Center, Denver, CO; Southwest Oncology Group Statistical Center, San Antonio, TX; Puget Sound Oncology Consortium, Seattle, WA; and University of California, Davis Cancer Center, Sacramento, CA
  • Jason McCoy
    From the University of Colorado Health Sciences Center, Denver, CO; Southwest Oncology Group Statistical Center, San Antonio, TX; Puget Sound Oncology Consortium, Seattle, WA; and University of California, Davis Cancer Center, Sacramento, CA
  • Howard West
    From the University of Colorado Health Sciences Center, Denver, CO; Southwest Oncology Group Statistical Center, San Antonio, TX; Puget Sound Oncology Consortium, Seattle, WA; and University of California, Davis Cancer Center, Sacramento, CA
  • Ana Carolina Xavier
    From the University of Colorado Health Sciences Center, Denver, CO; Southwest Oncology Group Statistical Center, San Antonio, TX; Puget Sound Oncology Consortium, Seattle, WA; and University of California, Davis Cancer Center, Sacramento, CA
  • Paul Gumerlock
    From the University of Colorado Health Sciences Center, Denver, CO; Southwest Oncology Group Statistical Center, San Antonio, TX; Puget Sound Oncology Consortium, Seattle, WA; and University of California, Davis Cancer Center, Sacramento, CA
  • Paul A. Bunn
    From the University of Colorado Health Sciences Center, Denver, CO; Southwest Oncology Group Statistical Center, San Antonio, TX; Puget Sound Oncology Consortium, Seattle, WA; and University of California, Davis Cancer Center, Sacramento, CA
  • Wilbur A. Franklin
    From the University of Colorado Health Sciences Center, Denver, CO; Southwest Oncology Group Statistical Center, San Antonio, TX; Puget Sound Oncology Consortium, Seattle, WA; and University of California, Davis Cancer Center, Sacramento, CA
  • John Crowley
    From the University of Colorado Health Sciences Center, Denver, CO; Southwest Oncology Group Statistical Center, San Antonio, TX; Puget Sound Oncology Consortium, Seattle, WA; and University of California, Davis Cancer Center, Sacramento, CA
  • David R. Gandara
    From the University of Colorado Health Sciences Center, Denver, CO; Southwest Oncology Group Statistical Center, San Antonio, TX; Puget Sound Oncology Consortium, Seattle, WA; and University of California, Davis Cancer Center, Sacramento, CA

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<jats:sec><jats:title>Purpose</jats:title><jats:p> Bronchioloalveolar carcinoma (BAC) and adenocarcinomas with BAC features seem to be increasing in incidence, particularly in younger, never-smoking women. Epidermal growth factor receptor (EGFR) inhibitors demonstrated response rates of 20% to 30% in patients with advanced BAC subtypes, but selection methods for patient therapy are not established. </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> EGFR and HER2 gene copy numbers were assessed by fluorescence in situ hybridization (FISH) in 81 patients treated with gefitinib 500 mg/d (Southwest Oncology Group protocol S0126) and were correlated to treatment outcome. Tumors were classified into two main strata: FISH-positive (high polysomy/gene amplification) and FISH-negative (disomy/low polysomy). </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> In 81 patients, the median survival time for EGFR/FISH-negative patients was 8 months and not yet reached for FISH-positive patients (but approaching 18 months; hazard ratio [HR] = 2.02; P = .042). Median progression-free survival time for EGFR/FISH-positive patients was 9 months versus 4 months for the FISH-negative patients (HR = 1.67; P = .072). In multivariate analysis, EGFR copy number by FISH remained a significant predictive factor for survival after accounting for smoking status, sex, histology, and performance status. Fifty-five patients were evaluated for response using Response Evaluation Criteria in Solid Tumors Group, and 12 of 19 EGFR/FISH-positive patients (63%) demonstrated disease control versus 14 (39%) of 36 patients in the FISH-negative group (P = .087). No association was found between HER2 gene copy number and response (n = 39 patients) or survival (n = 56 patients; P > .10). </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Increased EGFR gene copy number detected by FISH is associated with improved survival after gefitinib therapy in patients with advanced BAC, suggesting FISH methodology can be used to assess survival potential in patients treated with EGFR tyrosine kinase inhibitors. </jats:p></jats:sec>

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