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Gefitinib Therapy in Advanced Bronchioloalveolar Carcinoma: Southwest Oncology Group Study S0126

Howard L. West, Wilbur A. Franklin, Jason McCoy, Paul H. Gumerlock, Ralph Vance, Derick H.M. Lau, Kari Chansky, John J. Crowley, David R. Gandara

From the Swedish Cancer Institute/Puget Sound Oncology Consortium; Southwest Oncology Group Statistical Center, Seattle, WA; University of Colorado, Denver, CO; University of California, Davis, Sacramento, CA; and the University of Mississippi Medical Center, Jackson, MS

Address reprint requests to Bonnie Granados, Southwest Oncology Group (S0126), Operations Office, 14980 Omicron Dr, San Antonio, TX 78245-3217; e-mail: bgranados{at}swog.org

PURPOSE: Advanced bronchioloalveolar carcinoma (BAC) is a distinct subtype of non–small-cell lung cancer (NSCLC) for which there is currently no optimal therapy. Based on preclinical and clinical data suggesting relevance of the epidermal growth factor receptor (EGFR) axis in BAC, the Southwest Oncology Group initiated a phase II trial (S0126) to evaluate the EGFR tyrosine kinase inhibitor gefitinib in chemotherapy-naïve and chemotherapy-pretreated patients with advanced BAC.

METHODS: A total of 136 eligible and assessable patients (101 untreated, 35 previously treated) received gefitinib 500 mg daily until progression or prohibitive toxicity.

RESULTS: The median age was 68.0 years (range, 34.3 to 88.6); 51% were female; 89% had a performance status (PS) of 0% or 1% and 11% had a PS of 2. The Response Evaluation Criteria in Solid Tumors response rate was 17%, with 6% complete responses (CRs) among 69 previously untreated patients with measurable disease, and 9% with no CRs among 22 pretreated patients. Median survival was 13 months for both chemo-naïve (95% CI, 8 to 18) and previously treated patients (95% CI, 6 to 17). Overall survival at 3 years was 23% (95% CI, 14% to 32%). Toxicity consisted mainly of rash and diarrhea, but 2% of patients died of presumed interstitial lung disease. Exploratory subset analyses revealed improved survival among women (P = .031), patients developing a rash (P = .003), never-smokers (P = .061), and patients with a PS of 0 or 1 (P = .015).

CONCLUSION: Gefitinib is an active agent in advanced stage BAC. Several subsets demonstrate significantly improved clinical outcomes.

Supported in part by the following Public Health Service Cooperative Agreement Grants: CA38926, CA32102, CA46441, CA20319, CA35261, CA45450, CA74547, CA45808, CA35431, CA12644, CA14028, CA46368, CA35178, CA63844, CA45560, CA16385, CA11083, CA35119, CA45377, CA35090, CA58416, CA58861, CA37981, CA42777, CA67663, CA35176, CA63848, CA58882, CA46282, CA86780, CA22433, CA76448, CA67575, which were awarded by the National Cancer Institute, Department of Health and Human Services.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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