Skip to main content

A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer.

Publication ,  Journal Article
Soh, SX; Siddiqui, FJ; Allen, JC; Kim, GW; Lee, JC; Yatabe, Y; Soda, M; Mano, H; Soo, RA; Chin, T-M; Ebi, H; Yano, S; Matsuo, K; Niu, X ...
Published in: Oncotarget
June 20, 2017

BACKGROUND: A germline deletion in the BIM (BCL2L11) gene has been shown to impair the apoptotic response to tyrosine kinase inhibitors (TKIs) in vitro but its association with poor outcomes in TKI-treated non-small cell lung cancer (NSCLC) patients remains unclear. We conducted a systematic review and meta-analysis on both aggregate and individual patient data to address this issue. RESULTS: In an aggregate data meta-analysis (n = 1429), the BIM deletion was associated with inferior PFS (HR = 1.51, 95%CI = 1.06-2.13, P = 0.02). Using individual patient data (n = 1200), we found a significant interaction between the deletion and ethnicity. Amongst non-Koreans, the deletion was an independent predictor of shorter PFS (Chinese: HR = 1.607, 95%CI = 1.251-2.065, P = 0.0002; Japanese: HR = 2.636, 95%CI = 1.603-4.335, P = 0.0001), and OS (HR = 1.457, 95% CI = 1.063-1.997, P = 0.019). In Kaplan-Meier analyses, the BIM deletion was associated with shorter survival in non-Koreans (PFS: 8.0 months v 11.1 months, P < 0.0005; OS: 25.7 v 30.0 months, P = 0.042). In Koreans, the BIM deletion was not predictive of PFS or OS. MATERIALS AND METHODS: 10 published and 3 unpublished studies that reported survival outcomes in NSCLC patients stratified according to BIM deletion were identified from PubMed and Embase. Summary risk estimates were calculated from aggregate patient data using a random-effects model. For individual patient data, Kaplan-Meier analyses were supported by multivariate Cox regression to estimate hazard ratios (HRs) for PFS and OS. CONCLUSIONS: In selected populations, the BIM deletion is a significant predictor of shorter PFS and OS on EGFR-TKIs. Further studies to determine its effect on response to other BIM-dependent therapeutic agents are needed, so that alternative treatment strategies may be devised.

Duke Scholars

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

June 20, 2017

Volume

8

Issue

25

Start / End Page

41474 / 41486

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Polymorphism, Genetic
  • Mutation
  • Male
  • Lung Neoplasms
  • Humans
  • Female
  • ErbB Receptors
  • Disease-Free Survival
  • Bcl-2-Like Protein 11
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Soh, S. X., Siddiqui, F. J., Allen, J. C., Kim, G. W., Lee, J. C., Yatabe, Y., … Lim, W.-T. (2017). A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer. Oncotarget, 8(25), 41474–41486. https://doi.org/10.18632/oncotarget.17102
Soh, Sheila X., Fahad J. Siddiqui, John C. Allen, Go Woon Kim, Jae Cheol Lee, Yasushi Yatabe, Manabu Soda, et al. “A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer.Oncotarget 8, no. 25 (June 20, 2017): 41474–86. https://doi.org/10.18632/oncotarget.17102.
Soh SX, Siddiqui FJ, Allen JC, Kim GW, Lee JC, Yatabe Y, Soda M, Mano H, Soo RA, Chin T-M, Ebi H, Yano S, Matsuo K, Niu X, Lu S, Isobe K, Lee J-H, Yang JC, Zhao M, Zhou C, Lee J-K, Lee S-H, Lee JY, Ahn M-J, Tan TJ, Tan DS, Tan E-H, Ong ST, Lim W-T. A systematic review and meta-analysis of individual patient data on the impact of the BIM deletion polymorphism on treatment outcomes in epidermal growth factor receptor mutant lung cancer. Oncotarget. 2017 Jun 20;8(25):41474–41486.

Published In

Oncotarget

DOI

EISSN

1949-2553

Publication Date

June 20, 2017

Volume

8

Issue

25

Start / End Page

41474 / 41486

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Polymorphism, Genetic
  • Mutation
  • Male
  • Lung Neoplasms
  • Humans
  • Female
  • ErbB Receptors
  • Disease-Free Survival
  • Bcl-2-Like Protein 11