Publication: Role of BIM deletion polymorphism and BIM expression as predictive biomarkers to maximize the benefit of EGFR-TKI treatment in EGFR-Positive NSCLC
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Issued Date
2019
Resource Type
File Type
application/pdf
ISSN
15137368
Other identifier(s)
2-s2.0-85076993770
Rights Holder(s)
Scopus
Bibliographic Citation
Asian Pacific Journal of Cancer Prevention. Vol 20, No.12 (2019), p.3581-3589
Suggested Citation
Incharoen P., Charonpongsuntorn C., Saowapa C., Sirachainan E., Dejthevaporn T., Kampreasart K., Trachu N., Muntham D., Reungwetwattana T. Role of BIM deletion polymorphism and BIM expression as predictive biomarkers to maximize the benefit of EGFR-TKI treatment in EGFR-Positive NSCLC. Asian Pacific Journal of Cancer Prevention. Vol 20, No.12 (2019), p.3581-3589. doi:10.31557/APJCP.2019.20.12.3581 Retrieved from: https://hdl.handle.net/20.500.14740/5723
Abstract
Objective: BIM is a modulator of apoptosis that is triggered by EGFR-TKIs. This study evaluated the role of BIM deletion and its expression as predictor of EGFR-TKI treatment outcome. Methods: The medical record of 185 EGFR-positive advanced non-small cell lung cancer (NSCLC) patients with/ without EGFR-TKI treatment between 9/2012 and 12/2014 were retrospectively reviewed. BIM deletion polymorphism and expression were tested by RT-PCR and immunohistochemistry, respectively. Survival outcomes in EGFR-TKI-treated patients were analyzed according to treatment sequence and EGFR mutation. The correlation between BIM deletion polymorphism, expression, response rate (as a function of EGFR-TKI treatment) and schedule was also explored. Result: EGFR-TKIs were administered to 139 (75.1%) of the 185 patients: as the first-line in 52 (37.4%) patients and as later-line treatment in 87 (62.6%) patients. Median overall survival (mOS) was significantly longer in EGFR-TKIs treated patients (28.9 vs. 7.4 months, P<0.001). Among L858R-mutated patients, median progression-free survival (mPFS) was significantly longer in first-line EGFR TKI treatment than a later-line (12.6 vs. 6.3 months, P=0.03). BIM deletion polymorphism and expression was detected in 20.2% and 52.7%, respectively. Patients without BIM deletion polymorphism had a significantly longer mOS when treated with a first-line than with a later-line EGFR-TKI (28.9 vs. 20.7 months, P= 0.04). Patients without BIM expression had a significantly longer mPFS (9.6 vs. 7.3 months, P=0.01) better mOS and response rate (RR). Conclusion: BIM deletion polymorphism and expression may predict an EGFR-TKI response in patients with EGFR-positive during therapy. © 2019, Asian Pacific Organization for Cancer Prevention.
Subject(s)
BCL2L11 protein, human
BIM protein
EGFR protein, human
Epidermal growth factor receptor
Protein kinase inhibitor
Tumor marker
Aged
Apoptosis
Female
Genetics
Human
Lung tumor
Male
Metabolism
Middle aged
Non small cell lung cancer
Retrospective study
Single nucleotide polymorphism
Aged
Apoptosis
Bcl-2-Like Protein 11
Biomarkers, Tumor
Carcinoma, Non-Small-Cell Lung
ErbB Receptors
Female
Humans
Lung Neoplasms
Male
Middle Aged
Polymorphism, Single Nucleotide
Progression-Free Survival
Protein Kinase Inhibitors
Retrospective Studies
BIM protein
EGFR protein, human
Epidermal growth factor receptor
Protein kinase inhibitor
Tumor marker
Aged
Apoptosis
Female
Genetics
Human
Lung tumor
Male
Metabolism
Middle aged
Non small cell lung cancer
Retrospective study
Single nucleotide polymorphism
Aged
Apoptosis
Bcl-2-Like Protein 11
Biomarkers, Tumor
Carcinoma, Non-Small-Cell Lung
ErbB Receptors
Female
Humans
Lung Neoplasms
Male
Middle Aged
Polymorphism, Single Nucleotide
Progression-Free Survival
Protein Kinase Inhibitors
Retrospective Studies