TY - JOUR
T1 - Impact of HER2 expression on EGFR-TKI treatment outcomes in lung tumors harboring EGFR mutations
T2 - A HER2-CS study subset analysis
AU - Ohashi, Kadoaki
AU - Ninomiya, Kiichiro
AU - Yoshioka, Hiroshige
AU - Bessho, Akihiro
AU - Shibayama, Takuo
AU - Aoe, Keisuke
AU - Ishikawa, Nobuhisa
AU - Kozuki, Toshiyuki
AU - Kawai, Haruyuki
AU - Kuyama, Shoichi
AU - Miyoshi, Seigo
AU - Fujitaka, Kazunori
AU - Obata, Hideto
AU - Tsubata, Yukari
AU - Awaya, Yoshikazu
AU - Inoue, Masaaki
AU - Inoue, Koji
AU - Horita, Naokatsu
AU - Yanai, Hiroyuki
AU - Hotta, Katsuyuki
AU - Kiura, Katsuyuki
N1 - Funding Information:
This research was supported by a specific grant from the Japan Agency for Medical Research and Development (AMED, grant number: 17lk0103014h0005 ), which is funded by the Japanese government . No additional external funding was received for this study.
Funding Information:
Dr. Ohashi reports research funding from Boehringer Ingelheim, Novartis, AstraZeneca, Eli Lilly, MSD, and Daiichi-Sankyo outside the submitted work. Dr. Ohashi reports personal fees from AstraZeneca, MSD and Chugai pharmaceutical outside the submitted work.
Funding Information:
Dr. Shibayama reports research funding from Bristol-Myers Squibb outside the submitted work.
Funding Information:
Dr. Kozuki reports research funding from Chugai Pharmaceutical, AstraZeneca, Eli Lilly, Taiho pharmaceutical, Bristol-Myers Squibb and Merck Biopharma. Dr. Kozuki reports personal fees from Chugai Pharmaceutical, AstraZeneca, Eli Lilly, Taiho pharmaceutical, Bristol-Myers Squibb, Ono Pharmaceutical, MSD, Pfizer Japan, Kyowa Hakko Kirin, Boehringer Ingelheim, Nippon Kayaku, and Novartis outside the submitted work. Dr. Hotta reports grants and personal fees from AstraZeneca, Eli Lilly, Bristol-Myers Squibb, and Chugai pharmaceutical; personal fees from MSD, Ono Pharmaceutical, Nippon Kayaku, Taiho pharmaceutical, Novartis, Daiichi-Sankyo, Kyorin, Kyowa-Kirin, and Boehringer Ingelheim; and grants from Astellas outside the submitted work.
Funding Information:
Dr. Kiura has received honoraria from AstraZeneca, Eli Lilly, Novartis International, Taiho pharmaceutical, Pfizer Japan, Ono pharmaceutical, Bristol-Myers Squibb, MSD and Boehringer Ingelheim, advice fee from Daiichi Sankyo, research funding from KYORIN pharmaceutical, Daiichi Sankyo, Pfizer japan, Boehringer Ingelheim, MSD, Nippon Kayaku, Taiho Pharmaceutical, Ono Pharmaceutical, Chugai Pharmaceutical, and Bristol-Myers Squibb outside the submitted work.
PY - 2020/12
Y1 - 2020/12
N2 - Objectives: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatment for EGFR-mutated non-small-cell lung carcinoma (NSCLC); however, a biomarker to predict their efficacy has not been established. Although human epidermal growth factor receptor-2 (HER2) aberrations constitute a potential mechanism for acquired resistance to EGFR-TKIs, the impact of HER2 on EGFR-TKI treatment outcomes has not been systematically evaluated. In this post-hoc subgroup study, we examined the impact of HER2 on the effect of EGFR-TKIs in patients with NSCLC harboring EGFR mutations. Materials and Methods: Of 1126 patients with NSCLC enrolled into a prospective cohort study (HER2-CS study), we analyzed data of 356 (32 %) patients with EGFR-mutant tumors. HER2 protein expression levels were determined by immunohistochemistry (IHC) with the gastric cancer criteria. Patients were divided either to an HER2-P group (HER2-IHC2+/3+) or an HER2-N group (HER2-IHC0/1+). We primarily assessed differences in the time-to-treatment failure (TTF) of EGFR-TKI between the groups. Results: The HER2 scoring was as follows: IHC0 (n = 76, 21 %), IHC1+ (n = 199, 56 %), IHC2+ (n = 72, 20 %), and IHC3+ (n = 9, 3 %). The patients’ demographics were similar in the HER2-P and HER2-N groups. The HER2-P group showed a significantly shorter EGFR-TKI TTF than the HER2-N group (hazard ratio [HR]: 1.657, 95 % confidence interval [CI]: 1.076–2.552; median: 13.3 vs. 19.1 months). The magnitude of the negative impact of TTF was especially dependent on performance status (PS). HER2 expression significantly deteriorated the TTF in the subgroup with PS 2 (HR: 5.497, 95 % CI: 1.510–20.02), but not in that with better PS (HR: 1.437, 95 % CI: 0.899–2.298) (pinteraction = 0.015). Conclusion: In the current cohort, HER2 protein expression in EGFR-mutant NSCLC may have a negative impact on the effect of EGFR-TKIs, the effect of which was PS dependent.
AB - Objectives: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatment for EGFR-mutated non-small-cell lung carcinoma (NSCLC); however, a biomarker to predict their efficacy has not been established. Although human epidermal growth factor receptor-2 (HER2) aberrations constitute a potential mechanism for acquired resistance to EGFR-TKIs, the impact of HER2 on EGFR-TKI treatment outcomes has not been systematically evaluated. In this post-hoc subgroup study, we examined the impact of HER2 on the effect of EGFR-TKIs in patients with NSCLC harboring EGFR mutations. Materials and Methods: Of 1126 patients with NSCLC enrolled into a prospective cohort study (HER2-CS study), we analyzed data of 356 (32 %) patients with EGFR-mutant tumors. HER2 protein expression levels were determined by immunohistochemistry (IHC) with the gastric cancer criteria. Patients were divided either to an HER2-P group (HER2-IHC2+/3+) or an HER2-N group (HER2-IHC0/1+). We primarily assessed differences in the time-to-treatment failure (TTF) of EGFR-TKI between the groups. Results: The HER2 scoring was as follows: IHC0 (n = 76, 21 %), IHC1+ (n = 199, 56 %), IHC2+ (n = 72, 20 %), and IHC3+ (n = 9, 3 %). The patients’ demographics were similar in the HER2-P and HER2-N groups. The HER2-P group showed a significantly shorter EGFR-TKI TTF than the HER2-N group (hazard ratio [HR]: 1.657, 95 % confidence interval [CI]: 1.076–2.552; median: 13.3 vs. 19.1 months). The magnitude of the negative impact of TTF was especially dependent on performance status (PS). HER2 expression significantly deteriorated the TTF in the subgroup with PS 2 (HR: 5.497, 95 % CI: 1.510–20.02), but not in that with better PS (HR: 1.437, 95 % CI: 0.899–2.298) (pinteraction = 0.015). Conclusion: In the current cohort, HER2 protein expression in EGFR-mutant NSCLC may have a negative impact on the effect of EGFR-TKIs, the effect of which was PS dependent.
KW - Epidermal growth factor receptor mutations
KW - Human epidermal growth factor receptor-2
KW - Performance status
KW - Time-To-Treatment failure
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U2 - 10.1016/j.lungcan.2020.09.024
DO - 10.1016/j.lungcan.2020.09.024
M3 - Article
C2 - 33096420
AN - SCOPUS:85092920987
VL - 150
SP - 83
EP - 89
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
ER -