Asian Ethnicity and Adenocarcinoma Histology Continues to Predict Response to Gefitinib in Patients Treated for Advanced Non-Small Cell Carcinoma of the Lung in North America

Institutional series suggest specific subgroups of patients with non-small cell lung cancer (NSCLC); female, Asian, non-smokers, respond preferentially to gefitinib. Vancouver, BC, has a large Asian population and therefore is an ideal location to study this differential effect in a Western setting. We performed a retrospective analysis of patients treated with single agent gefitinib to determine if our experience reflects this observation. The pathology, radiology, laboratory investigations and clinical records of 61 patients treated with gefitinib at the BCCA between April 2002 and May 2004 were reviewed. Partial radiologic response was defined as per SWOG response criteria. Symptom responses were subjectively evaluated from chart review. Baseline characteristics at diagnosis; 62% Caucasian, 38% Asian, male 47%, smokers 67%, non-smokers 33%, ECOG 0/1 59%; tumor histology: 57% adenocarcinoma, 13% bronchoalveolar variant, 7% squamous, 23% other. Median treatment duration was 2 months. On radiologic review, 14 patients had a partial response, 25 had stable disease, 21 progressed, and 1 unknown. Twenty patients reported improved symptoms after ≥1 month, 23 had no change, 17 had symptom progression and 1 unknown. Toxicity was minimal; one patient had grade 3 hepatotoxicity that resolved with treatment cessation. Of the 14 radiological responders, 10 were Asian, 10 ECOG 0/1, 10 female, 8 non-smokers, 8 adenocarcinoma and 4 bronchoalveolar variant. At the BCCA, in a select number of patients with advanced NSCLC, gefitinib demonstrated radiologic evidence of anti-tumor activity and provided clinical benefit with minimal side effects. Most of the responders were patients of Asian ethnicity who had immigrated to Canada from China, Taiwan or Hong Kong. Our results suggest that the preferential response to gefitinib seen in the Asian population is preserved in a Western setting. The molecular basis of the improved response rate observed in the subset of female, Asian, non-smokers with adenocarcinoma or bronchoalveolar variant is currently being explored by gene sequencing studies at the British Columbia Cancer Agency Genome Science Centre.