Gefitinib (ZD1839) therapy for advanced bronchioloalveolar lung cancer (BAC): Southwest Oncology Group (SWOG) Study S0126

Abstract

7014 Background: BAC, a non-small cell lung cancer (NSCLC) subtype with distinctive clinical, pathologic, and radiographic characteristics, is increasing in incidence, especially among younger non-smoking women. Based on analysis of EGFR pathway expression patterns in BAC specimens from the SWOG Lung repository (Franklin, ASCO 2003) and anecdotal reports of prolonged complete response (CR) of advanced stage BAC to gefitinib, SWOG initiated S0126 to determine potential clinical, radiographic, pathologic, and molecular markers predictive of outcome under the influence of gefitinib therapy. Methods: 138 eligible patients (102 chemo-naive, 36 previously treated) were enrolled. Gefitinib 500 mg PO QD was given until evidence of progression or prohibitive toxicity. Results: Median age: 68.0 (range 34.3–88.6); 51% female; PS 0/1: 86%. Among 67 chemo-naive patients with measurable disease, the response rate (RR) by RECIST is 21%, with 6% CR. In 21 previously treated patients with measurable disease, RR is 10% (0% CR). Data on response by computer assisted image analysis will be presented. Median survival is 12 and 10 months for chemo-naïve and previously treated patients, respectively (p=NS). One year survival is ∼50% in each subgroup. Toxicity: acneiform rash and diarrhea as previously described; potential grade 5 toxicity in three cases of patients with increasing pulmonary consolidation, possible interstitial lung disease secondary to treatment versus disease progression and/or infection. Subset analyses show prolonged survival in females (16 vs 7 months, p=.003) and patients with rash (12 vs 5 months, p=.01). For molecular correlative studies, see Franklin: ASCO 04. Conclusions: 1) Gefitinib demonstrates single-agent activity in advanced BAC in both chemo-naïve and previously treated patients; 2) S0126 represents a large clinical and pathologic database of BAC, and as such is a resource for improving understanding of this unique NSCLC subset; 3) Further studies of EGFR inhibitors in BAC are warranted. (CA32102, CA38926) Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca Southwest Oncology Group