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01-10-2020 | NSCLC | Original Article

Efficacy of EGFR tyrosine kinase inhibitors in patients having EGFR-activating mutations with or without BIM polymorphisms

Authors: Ryo Ariyasu, Noriko Yanagitani, Kenichi Tadokoro, Toshikazu Yamaguchi, Ken Uchibori, Satoru Kitazono, Naoya Fujita, Ryohei Katayama, Makoto Nishio

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2020

Abstract

Purpose

Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer with BIM deletion polymorphism may have a limited response to EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, some results of previous reports are discordant. It is necessary to evaluate the relationship between BIM polymorphism and the efficacy of EGFR-TKIs.

Methods

We retrospectively analyzed patients treated with EGFR-TKIs. We collected serum samples from patients before EGFR-TKI administration. We analyzed BIM deletion polymorphism and BIM single nucleotide polymorphism in exon 5 c465C > T by the Invader^® assay.

Results

BIM deletion polymorphism was identified in 27 of 194 patients (13.9%). BIM single nucleotide polymorphism was identified in 29 of 194 patients (14.9%). The overall response ratio was 81.5% in patients with BIM deletion polymorphism, 89.7% with BIM single nucleotide polymorphism, and 83.6% with BIM wild type. Median progression-free survival was 10.3 months with BIM deletion polymorphism, 8.5 months with BIM single nucleotide polymorphism, and 10.4 months with BIM wild type. Overall survival was 38.4 months with BIM deletion polymorphism, 29.1 months with BIM single nucleotide polymorphism, and 31.6 months with BIM wild type. There were no significant differences between the groups in overall response ratio, progression-free survival, and overall survival.

Conclusions

BIM polymorphism does not affect EGFR-TKI efficacy.

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Shigematsu H, Lin L, Takahashi T et al (2005) Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 97:339–346. https://doi.org/10.1093/jnci/dji055CrossRefPubMed

Maemondo M, Inoue A, Kobayashi K et al (2010) Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 362:2380–2388. https://doi.org/10.1056/NEJMoa0909530CrossRefPubMed

Mitsudomi T, Morita S, Yatabe Y et al (2010) Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 11:121–128. https://doi.org/10.1016/S1470-2045(09)70364-XCrossRefPubMed

Zhou C, Wu Y-L, Chen G et al (2011) Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 12:735–742. https://doi.org/10.1016/S1470-2045(11)70184-XCrossRefPubMed

Wu Y-L, Zhou C, Hu C-P et al (2014) Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 15:213–222. https://doi.org/10.1016/S1470-2045(13)70604-1CrossRefPubMed

Inoue A, Yoshida K, Morita S et al (2016) Characteristics and overall survival of EGFR mutation-positive non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors: a retrospective analysis for 1660 Japanese patients. Jpn J Clin Oncol 46:462–467. https://doi.org/10.1093/jjco/hyw014CrossRefPubMedPubMedCentral

Morgillo F, Della Corte CM, Fasano M, Ciardiello F (2016) Mechanisms of resistance to EGFR-targeted drugs: lung cancer. ESMO Open 1:e000060. https://doi.org/10.1136/esmoopen-2016-000060CrossRefPubMedPubMedCentral

Cross DAE, Ashton SE, Ghiorghiu S et al (2014) AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov 4:1046–1061. https://doi.org/10.1158/2159-8290.CD-14-0337CrossRefPubMedPubMedCentral

Mok TS, Wu Y-L, Ahn M-J et al (2017) Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. N Engl J Med 376:629–640. https://doi.org/10.1056/NEJMoa1612674CrossRefPubMed

10.

Santoni-Rugiu E, Melchior LC, Urbanska EM et al (2019) Intrinsic resistance to EGFR-tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer: differences and similarities with acquired resistance. Cancers (Basel). https://doi.org/10.3390/cancers11070923CrossRef

11.

Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol 9:47–59. https://doi.org/10.1038/nrm2308CrossRefPubMed

12.

Gong Y, Somwar R, Politi K et al (2007) Induction of BIM is essential for apoptosis triggered by EGFR kinase inhibitors in mutant EGFR-dependent lung adenocarcinomas. PLoS Med 4:e294. https://doi.org/10.1371/journal.pmed.0040294CrossRefPubMedPubMedCentral

13.

Ng KP, Hillmer AM, Chuah CTH et al (2012) A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med 18:521–528. https://doi.org/10.1038/nm.2713CrossRefPubMed

14.

Lee JK, Shin J-Y, Kim S et al (2013) Primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with non-small-cell lung cancer harboring TKI-sensitive EGFR mutations: an exploratory study. Ann Oncol 24:2080–2087. https://doi.org/10.1093/annonc/mdt127CrossRefPubMed

15.

Nakagawa T, Takeuchi S, Yamada T et al (2013) EGFR-TKI resistance due to BIM polymorphism can be circumvented in combination with HDAC inhibition. Can Res 73:2428–2434. https://doi.org/10.1158/0008-5472.CAN-12-3479CrossRef

16.

Isobe K, Hata Y, Tochigi N et al (2014) Clinical significance of BIM deletion polymorphism in non-small-cell lung cancer with epidermal growth factor receptor mutation. J Thorac Oncol 9:483–487. https://doi.org/10.1097/JTO.0000000000000125CrossRefPubMedPubMedCentral

17.

Lee J-H, Lin Y-L, Hsu W-H et al (2014) Bcl-2-like protein 11 deletion polymorphism predicts survival in advanced non-small-cell lung cancer. J Thorac Oncol 9:1385–1392. https://doi.org/10.1097/JTO.0000000000000238CrossRefPubMed

18.

Zhao M, Zhang Y, Cai W et al (2014) The Bim deletion polymorphism clinical profile and its relation with tyrosine kinase inhibitor resistance in Chinese patients with non–small cell lung cancer. Cancer 120:2299–2307. https://doi.org/10.1002/cncr.28725CrossRefPubMed

19.

Cardona AF, Rojas L, Wills B et al (2016) BIM deletion polymorphisms in Hispanic patients with non-small cell lung cancer carriers of EGFR mutations. Oncotarget 7:68933–68942. https://doi.org/10.18632/oncotarget.12112CrossRefPubMedPubMedCentral

20.

Yuan J, Li B, Zhang N et al (2018) Clinical implications of the bim deletion polymorphism in advanced lung adenocarcinoma treated with gefitinib. Clin Lung Cancer 19:e431–e438. https://doi.org/10.1016/j.cllc.2018.02.007CrossRefPubMed

21.

Lee JY, Ku BM, Lim SH et al (2015) The BIM deletion polymorphism and its clinical implication in patients with EGFR-mutant non-small-cell lung cancer treated with EGFR tyrosine kinase inhibitors. J Thorac Oncol 10:903–909. https://doi.org/10.1097/JTO.0000000000000535CrossRefPubMed

22.

Wu S-G, Liu Y-N, Yu C-J et al (2016) Association of BIM deletion polymorphism with intrinsic resistance to EGFR tyrosine kinase inhibitors in patients with lung adenocarcinoma. JAMA Oncol 2:826–828. https://doi.org/10.1001/jamaoncol.2016.0016CrossRefPubMed

23.

Sun S, Yu H, Wang H et al (2017) Exploratory cohort study and meta-analysis of BIM deletion polymorphism in patients with epidermal growth factor receptor-mutant non-small-cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors. Onco Targets Ther 10:1955–1967. https://doi.org/10.2147/OTT.S126075CrossRefPubMedPubMedCentral

24.

Soh SX, Siddiqui FJ, Allen JC et al (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. https://doi.org/10.1832/oncotarget.17102CrossRefPubMedPubMedCentral

25.

Augis V, Airiau K, Josselin M et al (2013) A single nucleotide polymorphism in cBIM is associated with a slower achievement of major molecular response in chronic myeloid leukaemia treated with imatinib. PLoS ONE 8:e78582. https://doi.org/10.1371/journal.pone.0078582CrossRefPubMedPubMedCentral

26.

Olivier M (2005) The Invader^® assay for SNP genotyping. Mutat Res 573:103–110. https://doi.org/10.1016/j.mrfmmm.2004.08.016CrossRefPubMedPubMedCentral

27.

Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247. —https://doi.org/10.1016/j.ejca.2008.10.026CrossRefPubMed

28.

Ito Y, Umezu T, Tadokoro K et al (2019) BIM deletion polymorphism accounts for lack of favorable outcome in Japanese females with follicular lymphoma. Leuk Lymphoma 60:1283–1288. https://doi.org/10.1080/10428194.2018.1529310CrossRefPubMed

Title: Efficacy of EGFR tyrosine kinase inhibitors in patients having EGFR-activating mutations with or without BIM polymorphisms
Authors: Ryo Ariyasu
Noriko Yanagitani
Kenichi Tadokoro
Toshikazu Yamaguchi
Ken Uchibori
Satoru Kitazono
Naoya Fujita
Ryohei Katayama
Makoto Nishio
Publication date: 01-10-2020
Publisher: Springer Berlin Heidelberg
Keywords: NSCLC
Tyrosine Kinase Inhibitors
NSCLC
Tyrosine Kinase Inhibitors
Published in: Cancer Chemotherapy and Pharmacology / Issue 4/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-020-04136-7

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