1. Efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy as 1st line treatment for patients with non-small cell lung cancer harboring HER2 mutations: Results from LC-SCRUM-Asia.
- Author
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Kato Y, Udagawa H, Matsumoto S, Izumi H, Ohe Y, Kato T, Nishino K, Miyamoto S, Kawana S, Chikamori K, Shingyoji M, Sato Y, Takada Y, Toyozawa R, Azuma K, Tanaka Y, Sakai T, Shibata Y, Sugiyama E, Nosaki K, Zenke Y, Umemura S, Yoh K, Seike M, and Goto K
- Abstract
Introduction: HER2 mutations are reported to occur in 2%-5% of all cases of non-small cell lung cancer (NSCLC). The clinical outcomes in patients with HER2-mutant NSCLC treated with immune checkpoint inhibitors (ICIs) plus platinum-based chemotherapy as 1st line treatment still remain unclear., Methods: Using the large-scale clinico-genomic database of LC-SCRUM-Asia, the clinico-genomic characteristics and therapeutic outcomes of patients with HER2-mutant NSCLC were investigated., Results: Of the 15,251 patients with NSCLC enrolled in the LC-SCRUM-Asia database, tumor HER2 mutations were detected in 402 patients (2.6 %). The most common subtype of HER2 mutations was exon 20 in-frame insertions (79 %), followed in frequency by mutations in the tyrosine kinase domain other than Exon20ins (10 %) and mutations in extracellular domains (7 %). NSCLCs harboring HER2 mutations showed a higher tumor mutation burden (TMB) as compared with NSCLCs harboring EGFR mutations or ALK fusions (median: 4.22 vs. 2.54 and 2.52 mutation per megabase, respectively). Of the 402 patients, 268 patients had received platinum-based chemotherapy with ICIs (Chemo-ICI, n = 95) or without ICI (Chemo-alone, n = 173) as 1st line treatment. The progression-free survival (PFS) was significantly longer in the Chemo-ICI group as compared with the Chemo-alone group (median 8.5 vs. 6.3 months; HR [95 %CI]: 0.66 [0.50-0.88]; P < 0.005). Multivariate analysis identified use of ICIs in addition to platinum-based chemotherapy as an independent favorable prognostic factor for PFS. There was no significant difference in the overall survival between the patients of the Chemo-ICI and Chemo-alone groups (median 31.1 vs. 23.3 months; HR [95 %CI]: 0.80 [0.57-1.12], P = 0.20)., Conclusions: Addition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with HER2-mutant NSCLC. The relatively high TMB might be involved in the prolongation of the PFS in patients with HER2-mutant NSCLC receiving platinum-based chemotherapy with ICIs., 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 Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Amgen K.K., Taiho Pharmaceutical Co., Ltd. And MSD K.K. and honoraria for lectures from DAIICHI SANKYO COMPANY, LIMITED, CHUGAI PHARMACEUTICAL CO., LTD., Novartis Pharma K.K., Taiho Pharmaceutical Co. Ltd., Taiho Pharmaceutical Co. Ltd., and MSD K.K. outside the current study. Shingo Matsumoto reports grants from Merck, Chugai Pharmaceutical, MSD and Janssen Pharmaceutical and honoraria for lectures from Eli Lilly outside the current study. Hiroki Izumi reports grants from Amgen, Eisai, Takeda Pharmaceutical Co, Bristol-Myers Squibb Japan, Chugai, AstraZeneca, Ono Pharmaceutical Co, MSD and Merck outside the current study. Yuichiro Ohe reports grants from AstraZeneca, Chugai, Eli Lilly, Kirin, Sumitomo, Pfizer, Taiho, Novartis, Takeda, Daiichi-Sankyo and Janssen and honoraria for lectures from AstraZeneca, Chugai, Chugai, ONO, BMS, Boehringer Ingelheim, Bayer, Pfizer, MSD, Taiho, Nippon Kayaku, Kyowa Hakko Kirin, Eisai and Daiichi-Sankyo and payment for expert testimony from AstraZeneca, Chugai, ONO, BMS, Kyorin, Celltrion, Amgen, Nippon Kayaku, Boehringer Ingelheim, AnHeart Therapeutics Inc., PharmaMar outside the current study. Terufumi Kato reports grants from Abbvie, Amgen, Arrivent, AstraZeneca, Bayer, BeiGene, BluePrint, Bristol-Meyers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Gilead, GlaxoSmithKline, Haihe, Janssen, Merck KGaA, MSD, Novartis, Pfizer, Regeneron and Takeda and honoraria for lectures from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol-Meyers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck KGaA, MSD, Novartis, Ono, Pfizer, Taiho, and Takeda and other from AstraZeneca, BeiGene, Chugai, Daiichi-Sankyo, Janssen, Merck KGaA, MSD, Novartis, Pfizer outside the current study. His spouse is an employer of Eli Lilly. Kazumi Nishino reports grants from ONO PHARMACEUTICAL CO., LTD., TAIHO PHARMACEUTICAL CO., LTD., MSD, AbbVie, DAIICHI SANKYO COMPANY, LIMITED, Amgen, Eisai Co., Ltd., Sanofi K.K., Janssen Pharmaceutical K.K., Novartis Pharmaceuticals, Pfizer, Eli Lilly Japan, Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co.,Ltd., AstraZeneca, Merus NV, Gilead Sciences, CHUGAI PHARMACEUTICAL CO., LTD, Bayer Yakuhin, Ltd and AMGEN and honoraria for lectures from AstraZeneca, Nippon Boehringer Ingelheim, Eli Lilly Japan, MSD, Novartis Pharmaceuticals, Pfizer, Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., Bristol Myers Squibb, Nippon Kayaku, ONO PHARMACEUTICAL CO., LTD., Takeda Pharmaceutical Co.,Ltd., CHUGAI PHARMACEUTICAL CO., LTD, AMGEN, DAIICHI SANKYO COMPANY, LIMITED, Nippon Boehringer Ingelheim Co., Ltd. outside the current study. Yuki Sato reports honoraria for lectures from AstraZeneca, MSD, Novartis, Chugai Pharmaceutical, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Nippon Kayaku, Bristol Myers Squibb, Eli Lilly, Takeda, Kyowa Kirin, Daiichi Sankyo and Boehringer Ingelheim outside the current study. Ryo Toyozawa reports grants from Abbvie, Amgen, AnHeart Therapeutics, Daiichi Sankyo, Eli Lilly Japan, MSD, Novartis Pharma, Pfizer Japan and Takeda Pharmaceutical and honoraria for lectures from AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Eli Lilly Japan, MSD, Nippon Kayaku, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical and Thermo Fisher Scientific outside the current study. Koichi Azuma reports honoraria for lectures from AstraZeneca K.K., Ono Pharmaceutical, Chugai Pharmaceutical, MSD, Bristol-Myers Squibb and Takeda Pharmaceutical outside the current study. Tetsuya Sakai reports grants from Amgen, GlaxoSmithKline K.K, Daiichi Sankyo and NEC and honoraria for lectures from AstraZeneca, Novartis, Thermo Fisher Scientific, Takeda, OLYMPUS, Taiho, Chugai, MSD, Merck, Daiichi Sankyo, RIKEN GENESIS and Amco outside the current study. Yuji Shibata reports grants from MSD, Blueprint Medicines Corporation and Novartis and honoraria for lectures from Pfizer, Bristol-Myers Squibb, AstraZeneca, Ono Pharmaceutical Co., Ltd., Chugai, Takeda, Merck and Eli Lilly Japan outside the current study. Kaname Nosaki reports grants from Takeda, AstraZeneca, MSD K.K, Abbvie, Chugai Pharma, Daiichi Sankyo/UCB Japan and AnHeart Therapeutics and honoraria for lectures from AstraZeneca, Chugai Pharma, Lilly, MSD, Pfizer, Taiho Pharmaceutical, Janssen, Ono Pharmaceutical, Takeda, Novartis and Merck outside the current study. Yoshitaka Zenke reports grants from AstraZeneca, Daiichi-Sankyo, Amgen, GSK, Roche, MSD and Merck and honoraria for lectures from AstraZenca, Lilly, Chugai, Ono, Bristol-Meyers Squibb, Takeda, Boheringer-Ingelheim, Taiho, MSD, Novartis, Pfizer, Nihon Kayaku, Kyowa Kirin and Amgen outside the current study. Shigeki Umemura reports grants from Taiho pharmaceutical, Lilly and MSD and honoraria for lectures from MSD, Chugai Pharmaceutical, Takeda, AstraZeneca and Daiichi sankyo outside the current study. Kiyotaka Yoh reports grants from Abbvie, Amgen, ArriVent Biopharma, AstraZeneca, Boehringer Ingelheim, Chugai Pharma, Daiichi sankyo, Lilly, MSD, Taiho and Takeda and consulting fees from Boehringer Ingelheim and Abbvie and honoraria for lectures from Amgen, AstraZeneca, Bristol-Myers Squibb, Chugai Pharma, Daiichi sankyo, Kyowa kirin, Lilly, MSD, Ono Pharmaceutical and Takeda outside the current study. Masahiro Seike reports grants from Chugai Pharmaceutical, Eli Lilly, Kyowa Hakko Kirin, Taiho Pharmaceutical and Nippon Kayaku and honoraria for lectures from AstraZeneca, Chugai Pharmaceutical, Eli Lilly, Bristol-Myers Squibb, Pfizer, Nippon Kayaku, Daiichi-Sankyo, Merck Biopharma, MSD K.K, Taiho Pharmaceutical, Ono Pharmaceutical, Nippon Boehringer Ingelheim, Takeda Pharmaceutical, Kyowa Hakko Kirin, Novartis and Amgen inc outside the current study. Koichi Goto reports grants from Amgen K.K., Astellas Pharma Inc., AstraZeneca K.K., Nippon Boehringer Ingelheim Co., Ltd., Bristol-Myers Squibb K.K., CHUGAI PHARMACEUTICAL CO., LTD., DAIICHI SANKYO COMPANY, LIMITED, Eisai Co., Ltd., Janssen Pharmaceutical K.K., Kyowa Kirin Co., Ltd., Merck Biopharma Co., Ltd., MEDICAL& BIOLOGICAL LABORATORIES CO., LTD., MSD K.K., Novartis Pharma K.K., ONO PHARMACEUTICAL CO., LTD., Pfizer R&D Japan G.K., Sumitomo Pharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Bayer Yakuhin, Ltd., Merus N.V. and Takeda Pharmaceutical Co., Ltd. for the present manuscript. Koichi Goto also reports grants from Amgen Inc., AbbVie GK, AnHeart Therapeutics Inc., Blueprint Medicines Corporation., Craif Inc., Guardant Health Asia, Middle East & Africa, Inc, Haihe Biopharma Co., Ltd., Ignyta,Inc., Life Technologies Japan Ltd., Loxo Oncology, Inc., Lunit Inc., Precision Medicine Asia Co., Ltd., RIKEN GENESIS CO., LTD., Spectrum Pharmaceuticals, Inc., Sysmex Corporation., Turning Point Therapeutics,Inc. and honoraria for lectures from Amgen K.K., Amoy Diagnosties Co.,Ltd., AstraZeneca K.K., Bayer U.S., Bristol-Myers Squibb K.K., CHUGAI PHARMACEUTICAL CO., LTD., DAIICHI SANKYO COMPANY, LIMITED, Eisai Co., Ltd., Eli Lilly Japan K.K., Guardant Health Japan Corp., iTeos Therapeutics Inc., Janssen Pharmaceutical K.K., Thermo Fisher Scientific K.K., Merck Biopharma Co., Ltd., Nippon Kayaku Co.,Ltd., Novartis Pharma K.K., ONO PHARMACEUTICAL CO., LTD., Pharma Mar, S.A., RIKEN GENESIS CO., LTD., Taiho Pharmaceutical Co., Ltd. And Takeda Pharmaceutical Co., Ltd. And other from Amgen Inc., Amgen K.K., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., Bristol-Myers Squibb K.K., DAIICHI SANKYO COMPANY, LIMITED, Eli Lilly Japan K.K., GlaxoSmithKline K.K., Haihe Biopharma Co., Ltd., Janssen Pharmaceutical K.K. and SYNEOS HEALTH CLINICAL K.K. Other authors report no potential conflict of interest to disclose.., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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