Rebiopsy of patients (pts) with acquired resistance to epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC)

Abstract

8025 Background: The EGFR-TKIs erlotinib and gefitinib produce dramatic regressions of tumor in ∼ 70% of NSCLC patients with activating mutations in the EGFR-TK domain. After a median time to progression of ∼1 year, most pts have progressive disease. We undertook this study to search for mechanisms of “acquired resistance” to EGFR-TKIs, to determine the spectrum and frequency of secondary EGFR mutations which arose, and to determine the feasibility of rebiopsy in this setting. Methods: All pts had metastatic or recurrent NSCLC and prior treatment with EGFR-TKI and progressive disease while on EGFR-TKI. Pts must also have had an activating EGFR mutation OR radiographic response (RECIST or WHO) to EGFR-TKI OR significant and durable improvement in cancer-related symptoms as judged by patient's physician. Core biopsies were performed and studied for EGFR mutation (exons 18–21 including PCR-based test for T790M) and MET amplification. Results: From 8/04–12/08 98 pts were consented for rebiopsy and 85 underwent the procedure. Demographics Female/Male=59/39; median age 62 (range 28–88); smoking: never=59, former/current=39. Primary EGFR mutation was exon 19 del-39; exon 21 L858R-11, other/WT-28, pending-7. Median time on EGFR-TKI before biopsy was 12 months (7–28 months). Secondary EGFR mutations: T790M-33, other-2, none detected-31, indeterminate-10, pending-9. MET amplification in 2/16 studied to date. Conclusions: 1) Rebiopsy of patients with NSCLC and acquired resistance to EGFR TKIs is feasible and well-received by pts. 2) Knowledge of EGFR genotype including EGFR T790M and MET status can inform clinical trials of targeted therapies in this population 3) More complete annotation of MET status and exploratory analyses of profiles of specimens by metastatic sites and prior EGFR-TKI versus chemo and EGFR-TKI is ongoing. Supported by the Doris Duke Foundation, the LaBrecque Foundation, Steps for Breath, NIH, and an anonymous donor. No significant financial relationships to disclose.