TY - JOUR
T1 - Bronchioloalveolar pathologic subtype and smoking history predict sensitivity to gefitinib in advanced non-small-cell lung cancer
AU - Miller, Vincent A.
AU - Kris, Mark G.
AU - Shah, Neelain
AU - Patel, Jyoti
AU - Azzoli, Christopher
AU - Gomez, Jorge
AU - Krug, Lee M.
AU - Pao, William
AU - Rizvi, Naiyer
AU - Pizzo, Barbara
AU - Tyson, Leslie
AU - Venkatraman, Ennapadam
AU - Ben-Porat, Leah
AU - Memoli, Natalie
AU - Zakowski, Manreen
AU - Rusch, Valerie
AU - Heelan, Robert T.
PY - 2004
Y1 - 2004
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=1842509828&partnerID=8YFLogxK
U2 - 10.1200/JCO.2004.08.158
DO - 10.1200/JCO.2004.08.158
M3 - Review article
C2 - 15020612
AN - SCOPUS:1842509828
SN - 0732-183X
VL - 22
SP - 1103
EP - 1109
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 6
ER -