Abstract

BackgroundIn previous studies, the predictive role of BIM deletion polymorphism with respect to responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) has been controversial. The potential reasons for these inconsistent findings were unknown.MethodsData from CTONG0901 clinical trial and medical records of Guangdong Lung Cancer Institute (GLCI) were retrospectively pooled. A total of 194 and 141 EGFR‐mutant non‐small cell lung cancer (NSCLC) patients treated with first‐ and second‐generation EGFR‐TKIs were examined in the CTONG0901 and GLCI cohorts, respectively. Sixty‐eight patients were treated with third‐generation EGFR‐TKIs in the GLCI cohort. The BIM gene status was examined by next‐generation sequencing.ResultsThe frequency of BIM deletion polymorphism was 11.3% and 17.0% in CTONG0901 and GLCI cohorts, respectively. For first‐ and second‐generation EGFR‐TKIs in CTONG0901 cohort, objective response (ORR) was 54.5% in BIM deletion group versus 56.4% in wild‐type BIM group (P = .87); disease control rate (DCR) was 90.9% versus 88.4% (P = 1.00); progression‐free survival (PFS) was 10.5 versus 11.2 months (P = .59); and overall survival (OS) was 20.5 versus 20.5 months (P = .73). In GLCI cohort, ORR was 54.2% versus 60.7% (P = .55); DCR was 91.7% versus 96.6% (P = .27); PFS was 10.1 versus 11.6 months (P = .63); and OS was 58.5 versus 45.0 months (P = .93). For third‐generation EGFR‐TKIs, ORR was 18.2% versus 63.2% (P = .02); DCR was 81.8% versus 96.5%, (P = .12); PFS was 5.8 versus 9.0 months (P = .13); and OS was 30.0 versus 24.8 months (P = .85). Cox regression analysis showed that concomitant genetic alterations could adversely affect the response to EGFR‐TKIs, but not BIM deletion.ConclusionsThe presence of BIM deletion showed no relation to an impaired response to first‐, second‐, and third‐generation EGFR‐TKIs in NSCLC patients. The factors influencing the response of EGFR‐TKIs were concomitant genetic alterations, but not BIM deletion.

Highlights

  • In previous studies, the predictive role of BIM deletion polymorphism with respect to responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been controversial

  • Previous reports have indicated that the incidence of epidermal growth factor receptor (EGFR) mutations is high in Asian populations, reaching 30% in non-small cell lung cancer (NSCLC) patients and 50% in those with adenocarcinoma.[1]

  • Similar results were obtained in the Guangdong Lung Cancer Institute (GLCI) cohort (PFS: 10.1 vs 11.6 months, respectively, P = .63; overall survival (OS): 58.5 vs 45.0 months, respectively, P = .93) (Figures 2B and 2E)

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Summary

Introduction

The predictive role of BIM deletion polymorphism with respect to responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has been controversial. A total of 194 and 141 EGFR-mutant non-small cell lung cancer (NSCLC) patients treated with firstand second-generation EGFR-TKIs were examined in the CTONG0901 and GLCI cohorts, respectively. Previous reports have indicated that the incidence of epidermal growth factor receptor (EGFR) mutations is high in Asian populations, reaching 30% in non-small cell lung cancer (NSCLC) patients and 50% in those with adenocarcinoma.[1]. Other studies showed that BIM deletion polymorphism had no effect on the progression-free survival (PFS) or overall survival (OS) of patients treated with EGFR-TKI therapy.[13,17]

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