@article{24d131fe3b8947958d3ef73f5cedf1b0,
title = "Predictive value of EGFR mutation in non–small-cell lung cancer patients treated with platinum doublet postoperative chemotherapy",
abstract = "The mutation status of tumor tissue DNA (n = 389) of resected stage II-III non-squamous non–small-cell lung cancer (Ns-NSCLC) was analyzed using targeted deep sequencing as an exploratory biomarker study (JIPANG-TR) for the JIPANG study, a randomized phase III study of pemetrexed/cisplatin (Pem/Cis) vs vinorelbine/cisplatin (Vnr/Cis). The TP53 mutation, common EGFR mutations (exon 19 deletion and L858R), and KRAS mutations were frequently detected. The frequency of the EGFR mutation was significant among female patients. Patients with an EGFR mutation-positive status had a significantly shorter recurrence-free survival (RFS) time (24 mo vs not reached) (HR, 1.64; 95% CI, 1.22-2.21; P =.0011 for EGFR mutation status). Multivariable analysis identified both the pathological stage and EGFR mutation status as independent prognostic factors for RFS (HR, 1.78; 95% CI, 1.30-2.44; P =.0003 for disease stage; and HR, 1.57; 95% CI, 1.15-2.16; P =.0050 for EGFR mutation status). This study demonstrated that the EGFR mutation has either a poor prognostic or predictive impact on a poor response to postoperative chemotherapy with platinum doublet chemotherapy for stage II-III Ns-NSCLC patients. This result supports a role for mandatory molecular diagnosis of early-stage Ns-NSCLC for precision oncology and signifies the importance of adjuvant for the 3rd generation tyrosine kinase inhibitor rather than platinum-based chemotherapy. This study is registered with the UMIN Clinical Trial Registry (UMIN 000012237).",
keywords = "EGFR mutation, next-generation sequencing, non-squamous non–small-cell lung cancer, postoperative chemotherapy, prognosis",
author = "Toshiaki Takahashi and Kazuko Sakai and Hirotsugu Kenmotsu and Kiyotaka Yoh and Haruko Daga and Tatsuo Ohira and Tsuyoshi Ueno and Tadashi Aoki and Hidetoshi Hayashi and Koji Yamazaki and Yukio Hosomi and Chen-Yoshikawa, {Toyofumi F.} and Norihito Okumura and Yuichi Takiguchi and Akimasa Sekine and Tomohiro Haruki and Hiromasa Yamamoto and Yuki Sato and Hiroaki Akamatsu and Takashi Seto and Sho Saeki and Kenji Sugio and Makoto Nishio and Hidetoshi Inokawa and Nobuyuki Yamamoto and Kazuto Nishio and Masahiro Tsuboi",
note = "Funding Information: This research was supported by University Grants for Fundamental Research of Kindai University. We thank the participating patients and their families as well as all the site investigators and operations staff. We are grateful to data managers and other support staff of the West Japan Oncology Group, especially Mr. Sawa, Ms. Tanaka, Dr. Nakamura, and Dr. Takeda. The authors also thank Mr. Mine (Center for Instrumental Analyses Central Research Facilities, Kindai University Faculty of Medicine) and Ms. Kitano (Department of Genome Biology, Kindai University Faculty of Medicine) for technical assistance provided during the study. Funding Information: Toshiaki Takahashi reports grants and personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Ono Pharmaceutical, MSD, Pfizer, Nippon Boehringer Ingelheim, a grant from Amgen, and a personal fee from Roche Diagnostics, outside of the submitted work. Kazuko Sakai received personal fees from AstraZeneca, Bio‐Rad Laboratories, Chugai Pharmaceutical, Roche Diagnostics, Hitachi, outside of the submitted work. Hirotsugu Kenmotsu received grants and personal fees from Chugai Pharmaceutical, Novartis Pharma, Daiichi Sankyo, AstraZeneca, and personal fees from Ono Pharmaceutical, Boehringer Ingelheim, Eli Lilly, Kyowa Kirin, Bristol‐Myers Squibb, MSD, Pfizer, Taiho Pharmaceutical, outside of the submitted work. Kiyotaka Yoh received grants and personal fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, Taiho Pharmaceutical, grants from Pfizer, AbbVie, Bayer, Takeda Pharmaceutical, MSD, and personal fees from Bristol‐Myers Squibb, Chugai Pharmaceutical, Janssen, Novartis, Kyowa Kirin, Boehringer Ingelheim, outside of the submitted work. Haruko Daga received personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, MSD, Ono Pharmaceutical, Taiho Pharmaceutical, outside the submitted work. Hidetoshi Hayashi received grants and personal fees from AstraZeneca, Bristol‐Myers Squibb, Eli Lilly, MSD, Ono Pharmaceutical, Pfizer, Nippon Boehringer Ingelheim, Novartis Pharma, Merck Biopharma, Taiho Pharmaceutical, grants from AbbVie, AC Medical, Astellas Pharma, Daiichi Sankyo, Eisai, EPS Associates, GlaxoSmithKline, Japan Clinical Research Operations, Kyowa Kirin, Otsuka Pharmaceutical, Parexel International, PPD‐SNBL, Quintiles Transnational Japan, Takeda Pharmaceutical, Yakult Honsha, and a personal fee from Chugai Pharmaceutical, outside of the submitted work. Yuichi Takiguchi received grants and personal fees from Eli Lilly, Kyowa Kirin. Akimasa Sekine received personal fees from Eli Lilly, Ono Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Pfizer, outside the submitted work. Yuki Sato received personal fees from Novartis Pharma, Chugai Pharmaceutical, AstraZeneca, Pfizer, outside the submitted work. Hiroaki Akamatsu received grants and personal fees from Chugai Pharmaceutical, MSD, and personal fees from AstraZeneca, Nippon Boehringer Ingelheim, Bristol‐Myers Squibb, Eli Lilly, Novartis Pharma, Ono Pharmaceutical, Taiho Pharmaceutical, outside of the submitted work. Takashi Seto received grants and personal fees from Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly, MSD, Novartis Pharma, Pfizer, Takeda Pharmaceutical, grants from AbbVie, Kissei Pharmaceutical, Merck Biopharma, and personal fees from AstraZeneca, Bristol‐Myers Squibb, Covidien Japan, Kyowa Kirin, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Taiho Pharmaceutical, Thermo Fisher Scientific, outside of the submitted work, and is an employee of Precision Medicine Asia. Kenji Sugio received grants and personal fees from AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, Nippon Boehringer Ingelheim, Merck Sharp & Dohme Oncology, outside of the submitted work. Makoto Nishio received grants and personal fees from Ono Pharmaceutical, Bristol‐Myers Squibb, Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, MSD, Novartis, Daiichi Sankyo, Merck Serono, Takeda Pharmaceutical, Pfizer, Janssen, and personal fees from Boehringer Ingelheim, Nippon Kayaku, and consulting fees from AbbVie, Teijin Pharma, Ono Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, Bristol‐Myers Squibb, Takeda Pharmaceutical, Pfizer, Daiichi Sankyo, Eli Lilly, AstraZeneca, MSD outside the submitted work. Nobuyuki Yamamoto received grants and personal fees from AstraZeneca, Nippon Boehringer Ingelheim, Chugai Pharmaceutical, Eli Lilly, MSD, Ono Pharmaceutical, Pfizer, grants from Astellas Pharma, A2 Healthcare Corporation, Bristol‐Myers Squibb, CMIC Shift Zero, Daiichi Sankyo, IQVIA services Japan, PPD‐SNBL, Takeda Pharmaceutical, Taiho Pharmaceutical, and a personal fee from Novartis Pharma, outside the submitted work. Kazuto Nishio received grants and personal fees from Eli Lilly, Nippon Boehringer Ingelheim, grants from Ignyta, Korea Otsuka Pharmaceutical, Thoracic Oncology Research Group, North East Japan Study Group, and personal fees from Chugai Pharmaceutical, Eisai, Pfizer, Novartis Pharma, MSD, Ono Pharmaceutical, Bristol‐Myers Squibb, SymBio Pharmaceuticals, Life Technologies Japan, Solasia Pharma, Yakult Honsha, Roche Diagnostics, AstraZeneca, Otsuka Pharmaceutical, Sanofi, Guardant Health, Amgen, outside of the submitted work. Masahiro Tsuboi received grants and personal fees from AstraZeneca, Ono Pharmaceutical, Bristol‐Myers Squibb, Eli Lilly, MSD, grants from Nippon Boehringer Ingelheim, and personal fees from Novartis Pharma, Johnson and Johnson, Chugai Pharmaceutical, Teijin Pharma, Taiho Pharmaceutical, Medtronic Japan, outside the submitted work. The remaining authors have declared no conflicts of interest. Publisher Copyright: {\textcopyright} 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.",
year = "2021",
doi = "10.1111/cas.15171",
language = "English",
journal = "Cancer Science",
issn = "1347-9032",
publisher = "Wiley-Blackwell",
}
