Concomitant Genetic Alterations Having Greater Impact on the Clinical Benefit of EGFR-TKIs in EGFR-mutant Advanced NSCLC Than BIM Deletion Polymorphism

Overview

Journal Clin Transl Med

Publisher Wiley

Specialty General Medicine

Date 2020 Jun 9

PMID 32508032

Citations 4

Authors

Si-Yang Liu

Jia-Ying Zhou

Wen-Feng Li

Hao Sun

Yi-Chen Zhang

Hong-Hong Yan

Zhi-Hong Chen

Chun-Xiang Chen

Jun-Yi Ye

Jin-Ji Yang

Qing Zhou

Xu-Chao Zhang

Yi-Long Wu

Affiliations

Soon will be listed here.

Abstract

Background: 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. The potential reasons for these inconsistent findings were unknown.

Methods: Data 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.

Results: The 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.

Conclusions: The 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.

Citing Articles

Efficacy of osimertinib in a metastatic lung adenocarcinoma patient harboring somatic delL747_S752 and germline deletion polymorphism: a case report and literature review.

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PMID: 36388025 PMC: 9641130. DOI: 10.21037/tcr-22-1050.

Prognostic Value of BIM Deletion in EGFR-Mutant NSCLC Patients Treated with EGFR-TKIs: A Meta-Analysis.

Lv F, Sun L, Yang Q, Pan Z, Zhang Y Biomed Res Int. 2021; 2021:3621828.

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Mechanisms and management of 3rd‑generation EGFR‑TKI resistance in advanced non‑small cell lung cancer (Review).

He J, Huang Z, Han L, Gong Y, Xie C Int J Oncol. 2021; 59(5).

PMID: 34558640 PMC: 8562388. DOI: 10.3892/ijo.2021.5270.

Concomitant genetic alterations having greater impact on the clinical benefit of EGFR-TKIs in EGFR-mutant advanced NSCLC than BIM deletion polymorphism.

Liu S, Zhou J, Li W, Sun H, Zhang Y, Yan H Clin Transl Med. 2020; 10(1):337-345.

PMID: 32508032 PMC: 7240862. DOI: 10.1002/ctm2.12.

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