Clinical outcomes in patients with non-small cell lung cancer harboring EGFR Exon20 in-frame insertions in the near-loop and far-loop: Results from LC-SCRUM-Asia.

Autor: Okahisa M; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Cancer Medicine, Cooperative Graduate School, The Jikei University Graduate School of Medicine, Tokyo, Japan., Udagawa H; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Matsumoto S; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Kato T; Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan., Yokouchi H; Department of Respiratory Medicine, Hokkaido Cancer Center, Sapporo, Japan., Furuya N; Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan., Kanemaru R; Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan., Toyozawa R; Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan., Nishiyama A; Divisions of Medical Oncology, Kanazawa University Hospital, Kanazawa, Japan., Ohashi K; Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan., Miyamoto S; Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan., Nishino K; Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan., Nakamura A; Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan., Iwama E; Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Niho S; Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University, Mibu, Japan., Oi H; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Sakai T; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Shibata Y; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Izumi H; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Sugiyama E; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Nosaki K; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Umemura S; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Zenke Y; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Yoh K; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Kah Mun Low G; Medical Affairs, Janssen Asia Pacific, a division of Johnson & Johnson International (Singapore) Pte. Ltd, Singapore., Zhuo J; Statistics and Decision Science, Janssen China Research & Development, China., Goto K; Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan. Electronic address: kgoto@east.ncc.go.jp.
Jazyk: angličtina
Zdroj: Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2024 May; Vol. 191, pp. 107798. Date of Electronic Publication: 2024 Apr 23.
DOI: 10.1016/j.lungcan.2024.107798
Abstrakt: Objectives: In this study, we explored the clinical outcomes of non-small cell lung cancer (NSCLC) patients with EGFR Exon20 in-frame insertions (Exon20ins), and the impact of the location of Exon20ins on these clinical outcomes.
Materials and Methods: The efficacies of current systemic therapies in NSCLC patients harboring Exon20ins were investigated using a large-scale clinico-genomic database of LC-SCRUM-Asia, and compared with that of amivantamab in the CHRYSALIS trial.
Results: Of the 11,397 patients enrolled in LC-SCRUM-Asia, Exon20ins were detected in 189 patients (1.7 %). Treatment with classical EGFR tyrosine-kinase inhibitors (classical TKIs) was associated with a significantly shorter progression-free survival (PFS) in NSCLC patients with Exon20ins as compared with Exon19 deletions and L858R. Post platinum-based chemotherapy, classical TKIs and immune checkpoint inhibitors (ICIs) were associated with a shorter PFS than with docetaxel in patients with Exon20ins (HR [95 % CI]; TKIs vs docetaxel, 2.16 [1.35-3.46]; ICIs vs docetaxel, 1.49 [1.21-1.84]). Patients treated with amivantamab in the CHRYSALIS trial showed a risk reduction in PFS and overall survival as compared with LC-SCRUM-Asia patients treated with docetaxel, classical TKIs, or ICIs. Among the 189 patients, Exon20ins were classified as near-loop or far-loop insertions in 115 (61 %) and 56 (30 %) patients, respectively. Treatment with osimertinib was associated with a longer PFS in patients with Exon20ins in near-loop as compared with far-loop (median, 5.6 vs. 2.0 months; HR [95 % CI], 0.22 [0.07-0.64]).
Conclusions: After platinum-based chemotherapy, classical TKIs and ICIs are less effective in NSCLC patients with Exon20ins, and amivantamab may be a promising targeted therapy. There is a possibility that the location of Exon20ins has an impact on the efficacy of TKIs.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hibiki Udagawa reports grants from Takeda and Boehringer Ingelheim outside the current study. Shingo Matsumoto reports grants from Chugai Pharmaceutical, MSD and Janssen Pharmaceutical and honoraria for lectures from Merck and Eli Lilly outside the current study. Terufumi Kato reports grants from Abbvie, Amgen, AstraZeneca, BeiGene, BluePrint, Chugai, Daiichi-Sankyo, Eli Lilly, Haihe, Merck, MSD, Novartis, Pfizer, Regeneron, Takeda and Turning Point and honoraria for lectures from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Merck, MSD, Novartis, Ono, Pfizer, Taiho, and Takeda and other from AstraZeneca, BeiGene, Daiichi-Sankyo, Janssen Pharmaceutical, Merck, MSD, Novartis, Pfizer and Eli Lilly outside the current study. Hiroshi Yokouchi reports grants from AstraZeneca, Sanofi, Bristol-Myers Squibb, MSD, Takeda, Daiichi-Sankyo, Chugai Pharmaceutical, Abbvie, Amgen and Taiho and honoraria for lectures from AstraZeneca outside the current study. Naoki Furuya reports honoraria for lectures from Eli Lilly, AstraZeneca, Boehringer Ingelheim, Chugai, Bristol Myers Squibb, Taiho, Pfizer and Novartis. Ryo Toyozawa reports grants from Abbvie, Amgen, AnHeart Therapeutics, Daiichi-Sankyo, Eli Lilly, Novartis, Pfizer, and Takeda and honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Chugai, Eli Lilly, MSD, Novartis, Ono, Pfizer, Taiho, and Takeda outside the current study. Kadoaki Ohashi reports grants from Amgen, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eli Lilly and Novartis and honoraria for lectures from AstraZeneca, Chugai, Eli Lilly, Kyowa Kirin and Novartis and other from Momotaro-gene, Genentech and Novartis outside the current study. Kazumi Nishino reports grants from Abbvie, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Daiichi-Sankyo, Janssen Pharmaceutical, Merck, Merus, MSD, Novartis, Ono, Pfizer, Sanofi, Taiho, and Takeda and honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Eli Lilly, Janssen Pharmaceutical, Merk, Nippon Kayaku, Pfizer and Roche Diagnostics and other from AstraZeneca, Eli Lilly and Pfizer outside the current study. Atsushi Nakamura reports honoraria for lectures from AstraZeneca, Chugai, Eli Lilly, Taiho, Merck, Nippon Kayaku, Novartis, Pfizer and Thermo Fisher Scientific outside the current study. Eiji Iwama reports honoraria for lectures from AstraZeneca, Bayer, Chugai, Life Technologies, Novartis, Pfizer and Takeda outside the current study. Seiji Niho reports grants from Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Kyowa Kirin, Nippon Kayaku, Ono, Shionogi, Taiho and Teijin Pharma and honoraria for lectures from Amgen, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen Pharmaceutical, Kyorin, MSD, Nippon Kayaku, Novartis, Ono, Pfizer, Taiho and Takeda outside the current study. Tetsuya Sakai reports honoraria for lectures from AstraZeneca, Chugai, Merck, MSD, Novartis and Thermo Fisher Scientific outside the current study. Yuji Shibata reports grants from Blueprint, MSD and Novartis and honoraria for lectures from AstraZeneca, Bristol-Myers Squibb, Chugai, Eli Lilly, Merck, Ono, Pfizer and Takeda outside the current study. Hiroki Izumi reports grants from Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai, Eisai, MSD, Merck, Ono and Takeda outside the current study. Kaname Nosaki reports grants from Abbvie, AnHeart Therapeutics, AstraZeneca, Chugai, Daiichi Sankyo, MSD and Takeda and honoraria for lectures from AstraZeneca, Chugai, Eli Lilly, Janssen Pharmaceutical, Merck, MSD, Novartis, Ono, Pfizer, Taiho and Takeda and other from Abbvie and Daiichi Sankyo outside the current study. Shigeki Umemura reports honoraria for lectures from Chugai outside the current study. Yoshitaka Zenke reports grants from Amgen, AstraZeneca, Daiichi-Sankyo, GSK, Merck, MSD and Roche and honoraria for lectures from Amge, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Kyowa kirin, MSD, Nihon Kayaku, Novartis, Ono, Taiho and Takeda outside the current study. Kiyotaka Yoh reports grants from Abbvie, AstraZeneca, Chugai, Daiichi-Sankyo, Eli Lilly, MSD, Pfizer, Taiho and Takeda and honoraria for lectures from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Janssen Pharmaceutical, Kyowa kirin, Novartis and Taiho and other from Boehringer Ingelheim outside the current study. Grace K. M. Low was a full-time employee of Janssen when this study was performed and received long-term incentives from Janssen. She is currently not an employee of Janssen. Jianmin Zhuo is employed by Janssen China. Koichi Goto reports grants from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Blueprint, Craif, Daiichi-Sankyo, Eisai, Eli Lilly, Haihe Biopharma, Ignyta, Janssen Pharmaceutical, KISSEI PHARMACEUTICAL, Kyowa Kirin, Life Technologies Japan, Loxo Oncology, LSI Medience Corporation, MEDICAL&BIOLOGICAL LABORATORIES, Merck, Merus, MSD, Novartis, Ono, Pfizer, Precision Medicine Asia, RIKEN GENESIS, Sumitomo Pharma, Spectrum Pharmaceuticals, Sysmex Corporation, Taiho, Takeda, Turning Point Therapeutics and Xcoo and honoraria for lectures from Amgen, Amoy Diagnosties Co, AstraZeneca, Bayer, Boehringer Ingelheim, Blueprint, Daiichi-Sankyo, Eisai, Eli Lilly, Guardant Health Inc, Haihe Biopharma, Janssen Pharmaceutical, Medpace Japan, Merck, Nippon Kayaku, Novartis, Ono, Otsuka, RIKEN GENESIS CO, Taiho and Takeda and other from Amgen, Daiichi-Sankyo, Eli Lilly outside the current study.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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