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7003 Background: Erlotinib produces dramatic responses in a subset of patients with NSCLC. Mutations in the EGFR tyrosine kinase domain, EGFR amplification or polysomy and EGFR overexpression on immunohistochemistry have all been associated with sensitivity and benefit; pts with KRAS mutation are commonly resistant to this agent. These correlative studies were prospectively undertaken to characterize the ability of these markers to predict response rate, time to progression and survival in pts with BAC treated with the EGFR-TKI, erlotinib. Methods: One hundred and two patients received erlotinib as part of a phase II trial in BAC (Kris, Proc ASCO 2005); 84 had one or more correlative studies completed. Analysis of EGFR exons 19 and 21 (n=82) (Pao, et al PNAS 2004), EGFR IHC (n=62) (DAKO) was performed and EGFR copy number was determined by chromogenic in situ hybridization (CISH) (n=74) (Zymed); detection of ≥ 4 signals per cell was considered evidence of amplified copy number. KRAS exon 2 (n=79) testing was performed by direct sequencing. Fisher’s exact test was used to study the association of each feature in pts with partial response or no partial response. Time to progression and survival were analyzed with log-rank test. Results: See table below. Conclusions: 1) EGFR exon 19 or 21 mutation is a powerful predictor of response and TTP but not OS in pts with BAC treated with erlotinib. 2) CISH ≥4 is associated with response and improved TTP but not OS. 3) Patients with both EGFR mutation and amplification fare well supporting the concept of “oncogene addiction”; erlotinib should be considered as initial therapy in this population. 4) EGFR amplification without mutation is uncommon. 5) There is no clear utility of EGFR IHC in clinical decision making. 6) The presence of KRAS mutation predicts resistance to erlotinib. Supported, in part, by Genentech. Table: see text Table: see text
Miller et al. (Tue,) studied this question.