TY - JOUR
T1 - Trastuzumab emtansine for patients with non–small cell lung cancer positive for human epidermal growth factor receptor 2 exon-20 insertion mutations
AU - Iwama, Eiji
AU - Zenke, Yoshitaka
AU - Sugawara, Shunichi
AU - Daga, Haruko
AU - Morise, Masahiro
AU - Yanagitani, Noriko
AU - Sakamoto, Tomohiro
AU - Murakami, Haruyasu
AU - Kishimoto, Junji
AU - Matsumoto, Shingo
AU - Nakanishi, Yoichi
AU - Goto, Koichi
AU - Okamoto, Isamu
N1 - Funding Information:
This research was supported in part by the ‘Practical Research for Innovative Cancer Control’ funds from the Japan Agency for Medical Research and Development ( AMED , grant no. 20ck0106449h0003 ). T-DM1 was provided by Chugai Pharmaceutical (Chuo-ku, Tokyo, Japan).
Funding Information:
EI has received honoraria from Chugai Pharmaceutical, AstraZeneca, Lilly, Novartis and Pfizer. YZ has received honoraria and research funding from AstraZeneca ; honoraria from Chugai Pharmaceutical, Boehringer Ingelheim, Ono Pharmaceutical, Lilly and Bristol-Myers Squibb; and research funding from MSD and Merck . SS has received honoraria from Chugai Pharmaceutical, AstraZeneca, Boehringer Ingelheim, MSD, Bristol-Myers Squibb, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Lilly, Novartis, Kyowa Kirin and Yakult. HD has received honoraria from Chugai Pharmaceutical, AstraZeneca, Ono Pharmaceutical, Pfizer and Lilly. MM has received honoraria and research funding from Lilly and Boehringer Ingelheim as well as honoraria from Chugai Pharmaceutical, AstraZeneca, Pfizer, Ono Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo and MSD. NY has received honoraria from Chugai Pharmaceutical. TS has received honoraria from Chugai Pharmaceutical, AstraZeneca, Boehringer Ingelheim, MSD, Ono Pharmaceutical, Pfizer, Lilly, Novartis, Kyowa Kirin, Merck and Illumina. HM has received honoraria and research funding from Chugai Pharmaceutical , AstraZeneca , Takeda and Daiichi Sankyo ; honoraria from Pfizer, Ono Pharmaceutical, Bristol-Myers Squibb, MSD, Novartis, Lilly and Taiho Pharmaceutical; and research funding from Abbvie and IQvia . SM has received honoraria and research funding from Chugai Pharmaceutical , Lilly , Merck and Novartis ; honoraria from AstraZeneca, Riken Genesis, Amgen, Guardant Health and Janssen; and research funding from MSD . YN has received honoraria and research funding from Ono Pharmaceutical as well as honoraria from Chugai Pharmaceutical, AstraZeneca, Pfizer, Taiho Pharmaceutical, MSD, Boehringer Ingelheim and Kyorin. KG has received honoraria and research funding from Chugai Pharmaceutical , AstraZeneca , Lilly , Pfizer , Ono Pharmaceutical , Taiho Pharmaceutical , Boehringer Ingelheim , Daiichi Sankyo , MSD , Novartis , Amgen Astellas BioPharma , Amgen , Bristol-Myers Squibb , Eisai , Janssen , Kyowa Kirin and Takeda ; honoraria from Amoy Diagnostics, Guardant Health and Otsuka; and research funding from Merck NEC , Medical & Biological Laboratories , Sumitomo Dainippon Pharma , Sysmex , Kissei , Merck Serono , Astellas BioPharma , Loxo Oncology , Merus N.V. , Spectrum Pharmaceuticals , Ignyta and Shanghai Haihe Pharmaceutical . IO has received honoraria and research funding from Chugai Pharmaceutical , AstraZeneca , MSD , Lilly , Boehringer Ingelheim , Ono Pharmaceutical , Taiho Pharmaceutical and Bristol-Myers Squibb as well as honoraria from Pfizer and research funding from Astellas Astellas BioPharma , Novartis and AbbVie . JK declares no conflicts of interest.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2022/2
Y1 - 2022/2
N2 - Background: Human epidermal growth factor receptor 2 (HER2) mutations are present in ∼3% of patients with non–small cell lung cancer (NSCLC), with exon-20 insertions accounting for ∼90% of such HER2 mutations and having been identified as driver oncogenic alterations. Antibody–cytotoxic drug conjugates including trastuzumab deruxtecan have shown an excellent efficacy for NSCLC with HER2 mutations. We have now performed a phase II study to evaluate the efficacy of ado-trastuzumab emtansine (T-DM1) for NSCLC positive for HER2 exon-20 insertion mutations. Patients and methods: Eligible patients with HER2 exon-20 insertion mutations confirmed by next-generation sequencing or multiplex polymerase chain reaction platforms and a history of one or two lines of chemotherapy received T-DM1 (3.6 mg/kg) intravenously every 21 days. The primary end-point of the study was the objective response rate (ORR). Results: Between February 2019 and July 2020, 22 patients were enrolled in the study. A775_G776insYVMA was the most frequent HER2 exon-20 insertion mutation, accounting for 19 (86.4%) of the 22 patients. The ORR was 38.1% (90% confidence interval, 23.0–55.9%), and the disease control rate was 52.4%. The median duration of response was 3.5 months, and the median progression-free survival and median overall survival were 2.8 and 8.1 months, respectively. Toxicity was mild, with the frequency of adverse events of grade ≥3 being low. Conclusion: T-DM1 is a potential treatment option for patients with NSCLC with HER2 exon-20 insertion mutations. Further investigation of biomarkers for T-DM1 is warranted to improve its efficacy for NSCLC with such mutations. Clinical trial number: JapicCTI-194620
AB - Background: Human epidermal growth factor receptor 2 (HER2) mutations are present in ∼3% of patients with non–small cell lung cancer (NSCLC), with exon-20 insertions accounting for ∼90% of such HER2 mutations and having been identified as driver oncogenic alterations. Antibody–cytotoxic drug conjugates including trastuzumab deruxtecan have shown an excellent efficacy for NSCLC with HER2 mutations. We have now performed a phase II study to evaluate the efficacy of ado-trastuzumab emtansine (T-DM1) for NSCLC positive for HER2 exon-20 insertion mutations. Patients and methods: Eligible patients with HER2 exon-20 insertion mutations confirmed by next-generation sequencing or multiplex polymerase chain reaction platforms and a history of one or two lines of chemotherapy received T-DM1 (3.6 mg/kg) intravenously every 21 days. The primary end-point of the study was the objective response rate (ORR). Results: Between February 2019 and July 2020, 22 patients were enrolled in the study. A775_G776insYVMA was the most frequent HER2 exon-20 insertion mutation, accounting for 19 (86.4%) of the 22 patients. The ORR was 38.1% (90% confidence interval, 23.0–55.9%), and the disease control rate was 52.4%. The median duration of response was 3.5 months, and the median progression-free survival and median overall survival were 2.8 and 8.1 months, respectively. Toxicity was mild, with the frequency of adverse events of grade ≥3 being low. Conclusion: T-DM1 is a potential treatment option for patients with NSCLC with HER2 exon-20 insertion mutations. Further investigation of biomarkers for T-DM1 is warranted to improve its efficacy for NSCLC with such mutations. Clinical trial number: JapicCTI-194620
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U2 - 10.1016/j.ejca.2021.11.021
DO - 10.1016/j.ejca.2021.11.021
M3 - Article
C2 - 34959152
AN - SCOPUS:85121696215
VL - 162
SP - 99
EP - 106
JO - European Journal of Cancer and Clinical Oncology
JF - European Journal of Cancer and Clinical Oncology
SN - 0959-8049
ER -