TY - JOUR
T1 - Clinicomolecular Profile and Efficacy of Human Epidermal Growth Factor Receptor 2 (HER2)-Targeted Therapy for HER2-Amplified Advanced Biliary Tract Cancer
AU - Inoue, Kanae
AU - Nakamura, Yoshiaki
AU - Caughey, Bennett
AU - Zheng-Lin, Binbin
AU - Ueno, Makoto
AU - Furukawa, Masayuki
AU - Kawamoto, Yasuyuki
AU - Itoh, Shinji
AU - Umemoto, Kumiko
AU - Sudo, Kentaro
AU - Satoh, Taroh
AU - Mizuno, Nobumasa
AU - Kajiwara, Takeshi
AU - Fujisawa, Takao
AU - Bando, Hideaki
AU - Yoshino, Takayuki
AU - Strickler, John H.
AU - Morizane, Chigusa
AU - Bekaii-Saab, Tanios
AU - Ikeda, Masafumi
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2025/4/1
Y1 - 2025/4/1
N2 - PURPOSEThis study aimed to investigate the clinicomolecular profiles and the efficacy of human epidermal growth factor receptor 2 (HER2)-Targeted therapy in HER2-Amplified biliary tract cancer (BTC).METHODSThis study was an international collaboration that used combined data from the prospective SCRUM-Japan GOZILA and MONSTAR-SCREEN in Japan and retrospective reviews in the United States; patients with advanced BTC who had received systemic therapy were included. The clinicomolecular profiles were evaluated in an exploratory cohort, whereas the efficacy of HER2-Targeted therapy was assessed in a biomarker-selected cohort.RESULTSOf the 439 patients in the exploratory cohort, 43 (10%) had HER2 amplification. The frequencies of coalterations were higher in patients with HER2 amplification versus patients without HER2 amplification including HER2 mutations (26% v 5%, P <.001), TP53 mutations (84% v 61%, P =.003), and BRAF amplification (9% v 2%, P =.030). There were no KRAS mutations identified in patients with HER2-Amplified BTC. No significant difference in overall survival (OS) was observed between patients with and without HER2 amplification (median, 17.7 v 16.9 months; hazard ratio [HR], 0.95 [95% CI, 0.65 to 1.40]). Of the 60 patients with HER2-Amplified BTC in the biomarker-selected cohort (43 from Japan and 17 from the United States), the OS was significantly longer in 29 patients who received HER2-Targeted therapy than in those who did not receive HER2-Targeted therapy (median, 24.3 v 12.1 months; HR, 0.39 [95% CI, 0.23 to 0.82]). Multivariate analysis identified HER2-Targeted therapy as an independent prognostic factor for OS (HR, 0.29 [95% CI, 0.14 to 0.58]; P <.001).CONCLUSIONHER2 amplification was found in 10% of advanced BTC and was not identified as an independent prognostic factor for OS. Patients with HER2-Amplified BTC derive significant benefit from HER2-Targeted therapy.
AB - PURPOSEThis study aimed to investigate the clinicomolecular profiles and the efficacy of human epidermal growth factor receptor 2 (HER2)-Targeted therapy in HER2-Amplified biliary tract cancer (BTC).METHODSThis study was an international collaboration that used combined data from the prospective SCRUM-Japan GOZILA and MONSTAR-SCREEN in Japan and retrospective reviews in the United States; patients with advanced BTC who had received systemic therapy were included. The clinicomolecular profiles were evaluated in an exploratory cohort, whereas the efficacy of HER2-Targeted therapy was assessed in a biomarker-selected cohort.RESULTSOf the 439 patients in the exploratory cohort, 43 (10%) had HER2 amplification. The frequencies of coalterations were higher in patients with HER2 amplification versus patients without HER2 amplification including HER2 mutations (26% v 5%, P <.001), TP53 mutations (84% v 61%, P =.003), and BRAF amplification (9% v 2%, P =.030). There were no KRAS mutations identified in patients with HER2-Amplified BTC. No significant difference in overall survival (OS) was observed between patients with and without HER2 amplification (median, 17.7 v 16.9 months; hazard ratio [HR], 0.95 [95% CI, 0.65 to 1.40]). Of the 60 patients with HER2-Amplified BTC in the biomarker-selected cohort (43 from Japan and 17 from the United States), the OS was significantly longer in 29 patients who received HER2-Targeted therapy than in those who did not receive HER2-Targeted therapy (median, 24.3 v 12.1 months; HR, 0.39 [95% CI, 0.23 to 0.82]). Multivariate analysis identified HER2-Targeted therapy as an independent prognostic factor for OS (HR, 0.29 [95% CI, 0.14 to 0.58]; P <.001).CONCLUSIONHER2 amplification was found in 10% of advanced BTC and was not identified as an independent prognostic factor for OS. Patients with HER2-Amplified BTC derive significant benefit from HER2-Targeted therapy.
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U2 - 10.1200/PO-24-00718
DO - 10.1200/PO-24-00718
M3 - Article
C2 - 40209139
AN - SCOPUS:105003147848
SN - 2473-4284
VL - 9
JO - JCO Precision Oncology
JF - JCO Precision Oncology
M1 - e2400718
ER -
