Association between BIM Deletion Polymorphism and Efficacy of Osimertinib in Advanced EGFR T790M NSCLC Patients

Abstract

BCL-2-like 11 (BIM) deletion polymorphism (BIM-del) has been found to be associated with resistance to first-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, and is a poor prognostic factor for non-small-cell lung cancer (NSCLC) patients with EGFR mutations. Nevertheless, the impact of the BIM-del in advanced EGFR T790M NSCLC patients treated with third-generation EGFR-TKI, osimertinib, remains undetermined. The aim of this study is to explore the relationship among BIM-del and therapeutic efficacy of osimertinib in NSCLC patients with EGFR T790M. We totally recruited 137 Chinese Han NSCLC patients with EGFR T790M receiving osimertinib treatment from December 2015 to December 2019. Peripheral blood samples from these patients were collected to detect BIM-del by polymerase chain reaction. Clinical outcomes among patients with and without BIM-del were analyzed by Cox proportional hazards models. BIM-del was detected in 17.5% of all patients (24/137). The majority of patients were no more than 60 years (66%, 91/137), female (57%, 78/137), never smokers (81%, 111/137), ECOG performance status (PS) 0-1 (91%, 124/137), and had central nervous system (CNS) metastases (55%, 75/137). There were no associations between the BIM-del and clinical characteristics including age, sex, histology, smoking status, stage, ECOG PS score, and CNS metastases. Patients with BIM-del had a poor objective response rate compared to those without (29% vs. 57%, P = 0.012). BIM-del was associated with shorter progress free survival (PFS) and overall survival (OS). (PFS, 8.3 vs. 10.4 months, P = 0.042; OS, 14.8 vs. 23.4 months, P = 0.005). Multivariate analysis indicated that BIM-del was the independent prognostic factor for both PFS and OS in NSCLC patients with EGFR T790M receiving osimertinib. BIM-del was associated with inferior efficacy and may serve as a negative predictive biomarker to osimertinib in EGFR T790M NSCLC patients. Genotype analysis of the BIM-del in EGFR mutant patients may be helpful for guiding appropriate treatment.