Role of BIM Deletion Polymorphism and BIM Expression as Predictive Biomarkers to Maximize the Benefit of EGFR-TKI Treatment in EGFR-Positive NSCLC.

Pimpin Incharoen,Kaettipong Kampreasart,Chanchai Charonpongsuntorn,Narumol Trachu,Thanyanan Ruengwetwattana,Sakditat Saowapa,Thitiya Dejthevaporn,Dittapol Muntham,Ekaphop Sirachainan

doi:10.31557/apjcp.2019.20.12.3581

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.

Highlights

Lung cancer is one of the most common causes of malignancy-related death in the world, and most cases are non-small cell lung cancer (NSCLC) (Goldstraw et al, 2011; Jemal et al, 2011; Siegel et al, 2013)
There were no significant differences in the Median overall survival (mOS) and overall response rate (ORR) of the first-line and later-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs)
First-line EGFR-TKI treatment is the standard treatment for patients with EGFR-positive advanced NSCLC

Summary

Introduction

Lung cancer is one of the most common causes of malignancy-related death in the world, and most cases are non-small cell lung cancer (NSCLC) (Goldstraw et al, 2011; Jemal et al, 2011; Siegel et al, 2013). In NSCLC, systemic chemotherapy is the standard treatment for advanced disease. An activating mutation of the epidermal growth factor receptor (EGFR) gene is a common driver of NSCLC (Lynch et al, 2004). EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib, gefitinib and afatinib, have produced dramatic responses in patients with EGFR-positive NSCLC, as evidenced by significant improvements in the response rate (RR) and survival compared with patients treated with platinum doublet-based chemotherapy as first-line therapy. 2011) Currently, EGFR-TKI treatment is the standard first-line therapy for patients with NSCLC characterized by activating EGFR mutations. Whether sequence EGFR-TKI should be given as the first- or later-line treatment remains controversial

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Conclusion