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• This is the first study to evaluate the role of BIM status in NSCLC patients undergoing osimertinib treatment. • EGFR T790 M NSCLC patients with a BIM deletion polymorphism (BIM-del) had a poor objective response rate. • Patients with T790 M/BIM-del had a significantly shorter progression-free survival (PFS). • Multivariate cox analysis indicated that BIM-del was an independent prognostic factor for PFS. • Genotype analysis of the BIM-del may be helpful for guiding appropriate treatment. B-cell lymphoma 2-like 11 (BCL-2-like 11, BCL2L11 , also known as BIM) deletion polymorphism (BIM-del) has been associated with resistance to first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), and is a poor prognostic factor for EGFR-mutant non-small-cell lung cancer (NSCLC) patients. Nevertheless, the impact of BIM-del in advanced NSCLC patients treated with the third-generation EGFR-TKI osimertinib remains undetermined. This study aims to evaluate the relationship between BIM-del and therapeutic efficacy of osimertinib in pretreated NSCLC patients. Patients subjected to EGFR T790 M detection and prior osimertinib treatment between December 2015 and December 2019 in our hospital were enrolled in this study. Peripheral blood samples from these patients were collected to detect BIM-del by polymerase chain reaction. Cox proportional hazards models were used to analyze the clinical outcomes of patients with and without BIM-del. In total, 152 Chinese Han NSCLC patients—including 143 T790M-positive and nine T790M-negative patients—were enrolled. BIM-del was detected in only 17.5 % of T790M-positive patients (25/143). The majority of patients were aged <65 years (81.8 %, 117/143), were female (58.7 %, 84/143), were non-smokers (82.5 %, 118/143), had Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–1 (88.8 %, 129/143), and exhibited metastases in the central nervous system (CNS) (54.5 %, 78/143). 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 poorer objective response rate than those without (28.0 % versus 52.5 %, p = 0.026). Besides, BIM-del was associated with a significantly shorter progression-free survival (PFS) and a moderately shorter overall survival (OS) (8.3 versus 10.5 months, p = 0.031 and 15.9 versus 25.2 months, p = 0.1, respectively). Multivariate analysis indicated that BIM-del was an independent prognostic factor for PFS but not for OS in EGFR T790 M NSCLC patients. BIM-del is associated with poor clinical responses and outcomes, and might be a negative predictive and prognostic biomarker in EGFR T790 M NSCLC patients with osimertinib treatment. [ABSTRACT FROM AUTHOR] more...

Background Non–small-cell lung cancer (NSCLC) patients with both epidermal growth factor receptor ( EGFR ) positive mutation and B-cell chronic lymphocytic leukemia/lymphoma-like 11 (BIM) deletion polymorphism had a poor clinical response to EGFR -tyrosine kinase inhibitors (TKIs). The current study aimed to investigate the clinical efficacy and tolerability of EGFR -TKIs plus chemotherapy versus EGFR -TKIs alone as first-line treatment in advanced NSCLC patients with EGFR mutations and BIM deletion polymorphism. Methods A retrospective, non-randomized analysis was conducted. BIM deletion polymorphism was detected using polymerase chain reaction (PCR) analysis and direct sequencing of DNA from peripheral blood cells. Clinical characteristics, overall survival (OS), progress-free-survival (PFS), objective response rate (ORR) and treatment-related adverse events were compared between EGFR -TKIs alone versus EGFR -TKIs plus chemotherapy group. Results 65 patients were enrolled. 36 of them received EGFR -TKIs and 29 received EGFR -TKIs plus chemotherapy. EGFR -TKIs plus chemotherapy had significantly higher ORR than TKIs alone (65.5% vs. 38.9%, P  = 0.046). Median PFS was significantly longer in EGFR -TKIs plus chemotherapy group than in TKIs group (7.2 vs 4.7 m; P  = 0.008). Median OS was numerically longer in EGFR -TKIs plus chemotherapy group than in TKIs alone (18.5 vs 14.2 m; P  = 0.107). EGFR -TKIs plus chemotherapy was associated with more grade 3 or 4 hematological toxic effects than EGFR -TKIs alone. Conclusion EGFR -TKIs plus chemotherapy conferred a significantly higher ORR, prolonged PFS and numerically longer OS in advanced NSCLC patients with EGFR mutation and BIM deletion polymorphism. Further prospective studies are needed to validate these findings. [ABSTRACT FROM AUTHOR] more...