BIM deletion polymorphism to predict systemic treatment outcome in advanced non-small cell lung cancer.

Abstract

8055 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) and chemotherapies are treatments for EGFR mutant non-small cell lung cancer (NSCLC) patients. We explored the predictive factors for progression-free survival (PFS) and overall survival (OS) on first-line EGFR-TKIs and second-line chemotherapies in NSCLC patients. Methods: One hundred and six chemonaïve NSCLC patients who received first line gefitinib in a phase II study were prospectively followed until death. Clinical and molecular biomakers were correlated with PFS and OS. Results: The OS and PFS of first-line gefitinib treatment were 19.4 (95% CI 15.6-23.3) months and 7.4 (95% CI 6.7-8.1) months, respectively. Sixty-nine patients (65%) received subsequent second-line chemotherapy. Median PFS and OS of second-line chemotherapy were 5.7 (95% CI 4.8-6.6) and 15.1 (95% CI 10.5-20.2) months. Bcl-2-like protein 11 (also named as BIM) deletion polymorphism was found in 17 out of 101 (16.8%) patients tested. The median PFS from first-line gefitinib in patients carrying normal BIM and deletion polymorphism were 8.1 months and 3.6 months, respectively (p<0.001), and the median OS were 22.1 months and 14.1 months, respectively (p=0.041); in 44 patients with common EGFR mutations (del 19 or L858R), the PFS for patients carrying normal BIM and deletion polymorphism were 9.6 months and 7.4 months, respectively (p=0.034). A multivariate analysis suggested that BIM deletion polymorphism and EGFR mutational status were independent predictors for gefitinib PFS (hazard ratio 2.83, p=0.001, and 0.63, p=0.03, respectively). Conclusions: BIM deletion polymorphism predicts shorter PFS in EGFR mutation NSCLC patients treated with first line gefitinib.