TY - JOUR
T1 - A Phase II Study of Trastuzumab Emtansine in HER2-Positive Non–Small Cell Lung Cancer
AU - Hotta, Katsuyuki
AU - Aoe, Keisuke
AU - Kozuki, Toshiyuki
AU - Ohashi, Kadoaki
AU - Ninomiya, Kiichiro
AU - Ichihara, Eiki
AU - Kubo, Toshio
AU - Ninomiya, Takashi
AU - Chikamori, Kenichi
AU - Harada, Daijiro
AU - Nogami, Naoyuki
AU - Hirata, Taizo
AU - Hinotsu, shiro
AU - Toyooka, Shinichi
AU - Kiura, Katsuyuki
N1 - Funding Information:
This research was supported by a specific grant from the Japan Agency for Medical Research and Development, which is funded by the Japanese government. No additional external funding was received for this study. The investigational agent was kindly provided by Chugai Pharmaceuticals. All of the authors contributed to the writing of the study protocol. Kadoaki Ohashi, Katsuyuki Hotta, Taizo Hirata, Kiichiro Ninomiya, and Katsuyuki Kiura also participated in the trial design and setup. Kadoaki Ohashi, Katsuyuki Hotta, Kiichiro Ninomiya, and Katsuyuki Kiura calculated the required sample size.
Funding Information:
Disclosure: Dr. Hotta has received honoraria outside the current work from AstraZeneca, Ono Pharmaceutical, Astellas, Novartis, Bristol-Myers Squibb, Merck Sharp Dohme, Eli Lilly Japan, Daiichi-Sankyo Pharmaceutical, Boehringer-Ingelheim, Nihon Kayaku, Taiho Pharmaceutical, and Chugai Pharmaceutical. Dr. Hotta also has received research funding outside the current work from AstraZeneca, Boehringer-Ingelheim, Ono Pharmaceutical, Astellas, Novartis, Bristol-Myers Squib, Eli Lilly Japan, Merck Sharp Dohme, and Chugai Pharmaceutical. Dr. Ohashi has received a research grant from Novartis Pharmaceuticals Japan. Dr. Katsuyuki Kiura has received honoraria from Eli Lilly Japan, Nihon Kayaku, AstraZeneca, Daiichi-Sankyo Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, and Sanofi-Aventis. The remaining authors declare no conflict of interest.
Publisher Copyright:
© 2017 International Association for the Study of Lung Cancer
PY - 2018/2
Y1 - 2018/2
N2 - Trastuzumab emtansine (T-DM1), an anti–erb-b2 receptor tyrosine kinase 2 (HER2) antibody-drug conjugate, has been shown to significantly improve survival in HER2-positive breast cancer. We report a phase II trial of T-DM1 monotherapy in relapsed NSCLC with documented HER2 positivity (an immunohistochemistry [IHC] score of 3+, both an IHC score of 2+ and fluorescence in situ hybridization positivity, or exon 20 mutation). This study was terminated early because of limited efficacy. The demographic characteristics in the 15 assessable patients were as follows: median age, 67 years; male sex, 47%; performance status of 0 to 1, 80%; HER2 status IHC 3+, 33%; HER status IHC 2+/fluorescence in situ hybridization–positive, 20%; and exon 20 mutation, 47%. The median number of delivered cycles was 3 (range 1–11). One patient achieved a partial response with an objective response rate of 6.7% (90% confidence interval: 0.2–32.0). With a median follow-up time of 9.2 months, the median progression-free survival time and median survival time were 2.0 and 10.9 months, respectively. Grade 3 or 4 adverse events included thrombocytopenia (40%) and hepatotoxicity (20%) without any treatment-related deaths. T-DM1 had a limited efficacy for HER2-positive NSCLC in our cohort. Applying the concept of precision medicine to tumors appears challenging; thus, additional molecular approaches are warranted.
AB - Trastuzumab emtansine (T-DM1), an anti–erb-b2 receptor tyrosine kinase 2 (HER2) antibody-drug conjugate, has been shown to significantly improve survival in HER2-positive breast cancer. We report a phase II trial of T-DM1 monotherapy in relapsed NSCLC with documented HER2 positivity (an immunohistochemistry [IHC] score of 3+, both an IHC score of 2+ and fluorescence in situ hybridization positivity, or exon 20 mutation). This study was terminated early because of limited efficacy. The demographic characteristics in the 15 assessable patients were as follows: median age, 67 years; male sex, 47%; performance status of 0 to 1, 80%; HER2 status IHC 3+, 33%; HER status IHC 2+/fluorescence in situ hybridization–positive, 20%; and exon 20 mutation, 47%. The median number of delivered cycles was 3 (range 1–11). One patient achieved a partial response with an objective response rate of 6.7% (90% confidence interval: 0.2–32.0). With a median follow-up time of 9.2 months, the median progression-free survival time and median survival time were 2.0 and 10.9 months, respectively. Grade 3 or 4 adverse events included thrombocytopenia (40%) and hepatotoxicity (20%) without any treatment-related deaths. T-DM1 had a limited efficacy for HER2-positive NSCLC in our cohort. Applying the concept of precision medicine to tumors appears challenging; thus, additional molecular approaches are warranted.
KW - HER2
KW - Non–small cell lung cancer
KW - precision medicine
KW - trastuzumab emtansine
UR - http://www.scopus.com/inward/record.url?scp=85038848439&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038848439&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2017.10.032
DO - 10.1016/j.jtho.2017.10.032
M3 - Article
C2 - 29313813
AN - SCOPUS:85038848439
VL - 13
SP - 273
EP - 279
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
SN - 1556-0864
IS - 2
ER -