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Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
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BIM Gene Polymorphism Lowers the Efficacy of EGFR-TKIs in Advanced Nonsmall Cell Lung Cancer With Sensitive EGFR

Wu Feng Huang1, Ai Hua Liu, Hai Jin Zhao

  • 1From the Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Medicine
|August 20, 2015
PubMed

Insights

Non-BIM polymorphism in non-small cell lung cancer (NSCLC) patients with EGFR mutations is linked to longer progression-free survival (PFS) after EGFR-tyrosine kinase inhibitor (TKI) treatment. BIM polymorphism status is crucial for evaluating EGFR-targeted therapies.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacogenomics

Background:

  • Bcl-2-like 11 (BIM) triggered apoptosis is strongly associated with epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC).
  • The impact of BIM polymorphism on the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in NSCLC patients with EGFR mutations remains unclear.

Purpose of the Study:

  • To investigate the relationship between BIM polymorphism and the efficacy of EGFR-TKIs in advanced NSCLC patients with EGFR mutations.
  • To analyze the association of BIM polymorphism with objective response rates (ORRs), disease control rates (DCRs), and progression-free survival (PFS).

Main Methods:

  • A systematic literature search was conducted on electronic databases for eligible studies.
  • Data from 6 studies involving 773 patients were extracted and synthesized using a random-effect model.
  • Subgroup and sensitivity analyses were performed to assess the robustness of the findings.

Main Results:

  • Patients without BIM polymorphism showed significantly prolonged PFS compared to those with BIM polymorphism (HR 0.63, P=0.001).
  • Marginal, non-significant improvements in ORR (OR 1.71, P=0.097) and DCR (OR 1.56, P=0.153) were observed in patients without BIM polymorphism.
  • Subgroup analyses indicated that PFS benefits were predominantly seen in chemotherapy-naive and retrospective study cohorts.

Conclusions:

  • Non-BIM polymorphism is associated with longer PFS in advanced NSCLC EGFR-mutant patients treated with EGFR-TKIs.
  • BIM polymorphism status should be considered a key factor in future studies of EGFR-targeted agents for EGFR-mutant NSCLC.

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