BIM deletion polymorphism and the clinical outcome of patients with advanced NSCLC who received first-line platinum-based chemotherapy: Preliminary results.

Abstract

e22137 Background: The up-regulation of the proapoptotic polypeptide BIM was acquired during the cancer cell apoptosis induced either by cytotoxic agents or tyrosine kinase inhibitors (TKIs). Germline polymorphism of BIM deletion was associated with shorter progression free survival (PFS) in patients with EGFR-mutated lung cancer treated with EGFR-TKIs. The aim of this study is to investigate the correlation between the germline polymorphism of BIM deletion and the clinical outcome of patients with advanced NSCLC who received first-line platinum based chemotherapy. Methods: Since June of 2012, 140 consecutive chemo-naive advanced NSCLC patients who completed two cycles of first-line platinum based chemotherapy evaluable for response assessment were eligible for inclusion in Shanghai Pulmonary Hospital. Patients with stable disease were excluded in order to eliminate the indolent disease effect. Each patient’s genomic DNA was extracted from peripheral blood sample, then the genotype of the BIM deletion was performed using a single PCR reaction with the primers 5’-AATACCACAGAGGCCCACAG-3’ and 5’-GCCTGAAGGTGCTGAGAAAG-3’. Results: There are 49 patients who responded to chemotherapy (RE group) while 32 patients developed progressive disease (PD group). The clinical characteristics at baseline and chemotherapy regimens received were balanced between the two groups except for more stage IV patients noted in PD group (57 vs 58 years old of median age, 59% vs 62.5% of male, 63% vs 100% of stage IV in RE group and PD group respectively, and the predominant regimen with gemcitabine plus cisplatin in both groups). BIM deletion polymorphism were detected in 4 of RE group (4/49, 8.2%) and 8 of PD group (8/32, 25%) respectively, (odds ratio=0.267, 95% CI=0.073-0.977, P=0.046). Conclusions: The germline polymorphism of BIM deletion may contribute to the intrinsic resistance to the chemotherapy in advanced NSCLC.