Prognostic Value of BIM Deletion in EGFR-Mutant NSCLC Patients Treated with EGFR-TKIs: A Meta-Analysis

Area of Science:

• Oncology
• Genetics
• Pharmacology

Background:

• Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are standard treatments for EGFR-mutant non-small-cell lung cancer (NSCLC).
• Acquired resistance to EGFR-TKIs is a major clinical challenge in NSCLC treatment.
• A germline 2903-bp deletion polymorphism in the Bcl-2-like protein 11 (BIM) gene is associated with reduced BIM expression, potentially hindering TKI-induced apoptosis.

Purpose of the Study:

• To investigate the association between the BIM deletion polymorphism and treatment response in EGFR-mutant NSCLC patients receiving EGFR-TKIs.
• To clarify the clinical significance of the BIM deletion polymorphism as a predictive biomarker for EGFR-TKI therapy.

Main Methods:

• A comprehensive meta-analysis was conducted, searching major databases (PubMed, Embase, ClinicalTrials.gov) for relevant studies published before March 31, 2021.
• Data from 20 datasets, including 3003 patients with EGFR-mutant NSCLC, were analyzed.
• Random effects models were used to calculate hazard ratios (HRs) and odds ratios (ORs) for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR).

Main Results:

• The BIM deletion polymorphism was found in 15.8% of the analyzed patients.
• Patients with the BIM deletion exhibited significantly shorter PFS (HR = 1.35, P = 0.003) and a trend towards unfavorable OS (HR = 1.22, P = 0.068).
• The BIM deletion was associated with lower ORR (OR = 0.60, P = 0.004) and DCR (OR = 0.59, P = 0.014) compared to wild-type patients.

Conclusions:

• The BIM deletion polymorphism may contribute to resistance against EGFR-TKIs in EGFR-mutant NSCLC.
• This genetic variant shows potential as a predictive biomarker for treatment response to EGFR-TKIs, particularly in Asian populations.