Citations 2
Clinicomolecular Profile and Efficacy of Human Epidermal Growth Factor Receptor 2 (HER2)-Targeted Therapy for HER2 -Amplified Advanced Biliary Tract Cancer
Inoue, Kanae , Nakamura, Yoshiaki , Caughey, Bennett Adam , Zheng-Lin, Binbin , Ueno, Makoto , Furukawa, Masayuki , Itoh, Shinji , Umemoto, Kumiko , Sudo, Kentaro, Kajiwara, Takeshi , Fujisawa, Takao , Morizane, Chigusa , Caughey, Bennett , Kawamoto, Yasuyuki , Itoh, Shinji , Umemoto, Kumiko , Satoh, Taroh , Mizuno, Nobumasa , Kajiwara, Takeshi , Fujisawa, Takao , Bando, Hideaki , Yoshino, Takayuki , Strickler, John H , Morizane, Chigusa , Bekaii-Saab, Tanios S , Ikeda, Masafumi , Nakamura, Yoshiaki , Furukawa, Masayuki , Mizuno, Nobumasa , Bando, Hideaki , Yoshino, Takayuki , Strickler, John H. , Bekaii‐Saab, Tanios , Ikeda, Masafumi
JCO Precision Oncology | April 10, 2025 | Volume: No volume available | Issue: 9 | Pages: No page available
PURPOSE This 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). METHODS This 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. RESULTS Of 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). CONCLUSION HER2 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.
Comprehensive clinico-molecular profile and efficacy of anti-HER2 therapy for HER2 -amplified biliary tract cancer.
Inoue, Kanae , Zheng-Lin, Binbin , Ueno, Makoto, Furukawa, Masayuki , Itoh, Shinji , Umemoto, Kumiko , Sudo, Kentaro, Kajiwara, Takeshi , Morizane, Chigusa, Nakamura, Yoshiaki , Caughey, Bennett Adam , Ueno, Makoto , Kawamoto, Yasuyuki , Satoh, Taroh , Mizuno, Nobumasa , Fujisawa, Takao , Bando, Hideaki , Yoshino, Takayuki , Strickler, John H. , Bekaii‐Saab, Tanios , Morizane, Chigusa , Ikeda, Masafumi
Journal of Clinical Oncology | January 22, 2024 | Volume: 42 | Issue: 3_suppl | Pages: 544-544
10.1200/jco.2024.42.3_suppl.544
544 Background: Biliary tract cancer (BTC) is an aggressive malignancy with poor prognosis and limited treatment options. The prevalence of HER2 amplification in BTC has been reported to be 5-20%, and clinical trials suggested the clinical benefit of HER2-targeted treatment in this disease subpopulation. In a global collaboration, we investigated the comprehensive clinico-molecular characterization as well as the efficacy of anti-HER2 therapy in HER2-amplified BTC. Methods: Patients with advanced BTC who received systemic therapy were included from the GOZILA and MONSTAR studies in Japan and from the COLOMATE trial in the US. Genomic alterations were detected by tissue next-generation sequencing (NGS), including FoundationOne CDx and TempuslxT, and plasma circulating tumor DNA NGS including Guardant360 and FoundationOne Liquid CDx. The clinico-molecular characteristics were evaluated in an exploratory cohort comprised of patients from Japan, whereas the efficacy of anti-HER2 therapy was assessed in a biomarker selected cohort with patients from both Japan and the US. Results: Of 439 patients included in the exploratory cohort, 43 (10%) had HER2 amplification. BTC with primary tumor location in the gallbladder accounted for 58% of primary sites of patients with HER2 amplification. TP53 mutation (84% vs 61%, p=0.003) and BRAF amplification (9% vs 2%, p=0.030) were significantly more frequent in patients with HER2 amplification compared to those without, and no KRAS mutation co-occurred with HER2 amplification. There was no significant difference in overall survival (OS) between patients with and without HER2 amplification (17.7 months [M] vs 16.9 M, hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.65-1.40, p=0.799). Of 58 patients with HER2-amplified BTC included in the biomarker selected cohort (43 Japan, 15 US), 27 (47%) received anti-HER2 therapy. The median OS of patients treated with anti-HER2 therapy was significantly longer than that of patients who did not receive anti-HER2 therapy (24.3 M vs. 12.1 M, HR 0.43, 95% CI 0.23-0.82, p=0.011). Multivariate analysis also identified anti-HER2 therapy as an independent prognostic factor for OS (HR 0.42, 95% CI 0.20-0.85, p=0.015). Conclusions: HER2 amplifications were found in 10% of advanced BTC and did not represent an independent predictive factor for OS. Of clinical significance, patients with HER2-amplified BTC derive a significant benefit from anti-HER2 therapy.