Affiliation:
1. From the Thoracic Oncology Service, Departments of Medicine, Biostatistics, Pathology, Surgery, and Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY.
Abstract
PurposeGefitinib, 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 MethodsWe 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.ResultsOf 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 ≤ 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.ConclusionOur 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.
Publisher
American Society of Clinical Oncology (ASCO)
Reference30 articles.
1. Mendelsohn J: Blockade of receptors for growth factors: An anticancer therapy—The fourth annual Joseph H. Burchenal American Association for Cancer Research Clinical Research Award Lecture. Clin Cancer Res 6:747,2000-753,
2. Wakeling AE, Guy SP, Woodburn JR, et al: ZD1839 (Iressa): An orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res 62:5749,2002-5754,
3. ZD1839, a Selective Oral Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitor, Is Well Tolerated and Active in Patients With Solid, Malignant Tumors: Results of a Phase I Trial
4. Phase I Safety, Pharmacokinetic, and Pharmacodynamic Trial of ZD1839, a Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Five Selected Solid Tumor Types
5. Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor ZD1839 Is Generally Well-Tolerated and Has Activity in Non–Small-Cell Lung Cancer and Other Solid Tumors: Results of a Phase I Trial
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