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Title: 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
Authors: Soh, S.X
Siddiqui, F.J 
Allen, J.C 
Kim, G.W
Lee, J.C
Yatabe, Y
Soda, M
Mano, H
Soo, R.A 
Chin, T.-M 
Ebi, H
Yano, S
Matsuo, K
Niu, X
Lu, S
Isobe, K
Lee, J.-H
Yang, J.C
Zhao, M
Zhou, C
Lee, J.-K
Lee, S.-H
Lee, J.Y
Ahn, M.-J
Tan, T.J
Tan, D.S 
Tan, E.-H
Ong, S.T 
Lim, W.-T 
Keywords: BIM protein
epidermal growth factor receptor
age distribution
BIM gene
cancer prognosis
cancer staging
EGFR gene
gene deletion
gene frequency
gene linkage disequilibrium
genetic association
genetic variability
genotyping technique
Japanese (people)
Korean (people)
median survival time
non small cell lung cancer
overall survival
progression free survival
sex difference
single nucleotide polymorphism
survival prediction
systematic review
treatment outcome
Issue Date: 2017
Publisher: Impact Journals LLC
Citation: Soh, S.X, Siddiqui, F.J, Allen, J.C, Kim, G.W, Lee, J.C, Yatabe, Y, Soda, M, Mano, H, Soo, R.A, Chin, T.-M, Ebi, H, Yano, S, Matsuo, K, Niu, X, Lu, S, Isobe, K, Lee, J.-H, Yang, J.C, Zhao, M, Zhou, C, Lee, J.-K, Lee, S.-H, Lee, J.Y, Ahn, M.-J, Tan, T.J, Tan, D.S, Tan, E.-H, Ong, S.T, 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. ScholarBank@NUS Repository.
Abstract: 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. © Soh et al.
Source Title: Oncotarget
ISSN: 19492553
DOI: 10.18632/oncotarget.17102
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