Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer Journal Article

Authors: Miller, V. A.; Kris, M. G.; Shah, N.; Patel, J.; Azzoli, C.; Gomez, J.; Krug, L. M.; Pao, W.; Rizvi, N.; Pizzo, B.; Tyson, L.; Venkatraman, E.; Ben-Porat, L.; Memoli, N.; Zakowski, M.; Rusch, V.; Heelan, R. T.
Article Title: Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer
Abstract: Purpose: Gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, induces radiographic regressions and symptomatic improvement in patients with non-small-cell lung cancer (NSCLC). Phase II trials suggested female sex and adenocarcinoma were associated with response. We undertook this analysis to identify additional clinical and pathologic features associated with sensitivity to gefitinib. Patients and Methods: We reviewed medical records, pathologic material, and imaging studies of all 139 NSCLC patients treated on one of three consecutive studies of gefitinib monotherapy performed at our institution. We identified patients experiencing a major objective response and compared their clinical and pathologic features with the others. Univariate and multivariable analyses were performed on potential predictive features associated with sensitivity to gefitinib. Results: Of 139 patients, 21 (15%; 95% CI, 9% to 21%), experienced a partial radiographic response. Variables identified as significant in univariate analysis included adenocarcinoma versus other NSCLC (19% v 0%; P = .004), adenocarcinoma with bronchioloalveolar features versus other adenocarcinomas (38% v 14%; P < .001), never smoker status versus former/current (36% v 8%; P < .001), and Karnofsky performance status > 80% versus s 70% (22% v 8%; P = .03). Multivariable analysis revealed the presence of adenocarcinoma with any bronchioloalveolar features (P = .004) and being a never smoker (P = .006) were independent predictors of response. Conclusion: Our data suggest that individuals in whom gefitinib is efficacious are more likely to have adenocarcinomas of the bronchioloalveolar subtype and to be never smokers. These observations may provide clues to mechanisms determining sensitivity to this agent and suggest that NSCLC has a different biology in patients who never smoked and those with bronchioloalveolar carcinoma. © 2004 by American Society of Clinical Oncology.
Keywords: epidermal growth factor; adult; controlled study; aged; aged, 80 and over; middle aged; retrospective studies; major clinical study; clinical feature; review; advanced cancer; antineoplastic agents; antineoplastic agent; adenocarcinoma; cytology; lung non small cell cancer; carcinoma, non-small-cell lung; logistic models; lung neoplasms; smoking; pathology; protein tyrosine kinase; retrospective study; lung tumor; drug antagonism; medical record; gefitinib; lung carcinoma; multivariate analysis; protein-tyrosine kinases; quinazolines; drug sensitivity; statistical model; quinazoline derivative; lung lavage; bronchoalveolar lavage fluid; carcinoma, bronchogenic; lung alveolus; humans; human; male; female; priority journal; article
Journal Title: Journal of Clinical Oncology
Volume: 22
Issue: 6
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2004-03-15
Start Page: 1103
End Page: 1109
Language: English
DOI: 10.1200/jco.2004.08.158
PROVIDER: scopus
PUBMED: 15020612
Notes: J. Clin. Oncol. -- Cited By (since 1996):588 -- Export Date: 16 June 2014 -- CODEN: JCOND -- Source: Scopus
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MSK Authors
  1. Venkatraman Ennapadam Seshan
    285 Seshan
  2. Jorge Gomez
    26 Gomez
  3. Natalie Poppito Memoli
    7 Memoli
  4. Valerie W Rusch
    652 Rusch
  5. Lee M Krug
    211 Krug
  6. Christopher G Azzoli
    105 Azzoli
  7. Jyoti Patel
    7 Patel
  8. William Pao
    141 Pao
  9. Naiyer A Rizvi
    156 Rizvi
  10. Vincent Miller
    261 Miller
  11. Maureen F Zakowski
    275 Zakowski
  12. Mark Kris
    597 Kris
  13. Robert T Heelan
    79 Heelan
  14. Leslie Tyson
    50 Tyson
  15. Neelam Todi Shah
    6 Shah
  16. Barbara Pizzo
    31 Pizzo