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

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ORIGINAL ARTICLE

Efficacy of EGFR tyrosine kinase inhibitors in patients having EGFR‑activating mutations with or without BIM polymorphisms Ryo Ariyasu1 · Noriko Yanagitani1 · Kenichi Tadokoro2 · Toshikazu Yamaguchi2 · Ken Uchibori1 · Satoru Kitazono1 · Naoya Fujita3 · Ryohei Katayama3 · Makoto Nishio1  Received: 28 May 2020 / Accepted: 4 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 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. Keywords  BIM deletion polymorphism · BIM single nucleotide polymorphism · Non-small cell lung cancer · EGFR-TKI

Introduction Ryo Ariyasu and Noriko Yanagitani contributed equally to this work. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0028​0-020-04136​-7) contains supplementary material, which is available to authorized users. * Ryohei Katayama [email protected] * Makoto Nishio [email protected] 1



Department of Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, 3‑8‑31, Ariake, Koto‑ku, Tokyo 135‑8550, Japan

2



BML, INC, 1361‑1, Matoba, Kawagoe‑shi, Saitama 350‑1101, Japan

3

Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3‑8‑31, Ariake, Koto‑ku, Tokyo 135‑8550, Japan



Lung cancer is a leading cause of cancer-related death in the world. Approximately 30% of lung cancer cases in Japan are epidermal growth factor receptor (EGFR)-mutated cancers [1]. The treatment of advanced non-small cell lung cancer (NSCLC) has dramatically advanced during the past 2  decades. Identification of EGFR-activating mutations and EG