{"title":"人表皮生长因子受体2 （HER2）靶向治疗HER2扩增晚期胆道癌的临床分子特征和疗效","authors":"Kanae Inoue, Yoshiaki Nakamura, Bennett Caughey, Binbin Zheng-Lin, Makoto Ueno, Masayuki Furukawa, Yasuyuki Kawamoto, Shinji Itoh, Kumiko Umemoto, Kentaro Sudo, Taroh Satoh, Nobumasa Mizuno, Takeshi Kajiwara, Takao Fujisawa, Hideaki Bando, Takayuki Yoshino, John H Strickler, Chigusa Morizane, Tanios Bekaii-Saab, Masafumi Ikeda","doi":"10.1200/PO-24-00718","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the clinicomolecular profiles and the efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy in <i>HER2</i>-amplified biliary tract cancer (BTC).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Of the 439 patients in the exploratory cohort, 43 (10%) had <i>HER2</i> amplification. The frequencies of coalterations were higher in patients with <i>HER2</i> amplification versus patients without <i>HER2</i> amplification including <i>HER2</i> mutations (26% <i>v</i> 5%, <i>P</i> < .001), <i>TP53</i> mutations (84% <i>v</i> 61%, <i>P</i> = .003), and <i>BRAF</i> amplification (9% <i>v</i> 2%, <i>P</i> = .030). There were no <i>KRAS</i> mutations identified in patients with <i>HER2-</i>amplified BTC. No significant difference in overall survival (OS) was observed between patients with and without <i>HER2</i> amplification (median, 17.7 <i>v</i> 16.9 months; hazard ratio [HR], 0.95 [95% CI, 0.65 to 1.40]). Of the 60 patients with <i>HER2</i>-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 <i>v</i> 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]; <i>P</i> < .001).</p><p><strong>Conclusion: </strong><i>HER2</i> amplification was found in 10% of advanced BTC and was not identified as an independent prognostic factor for OS. Patients with <i>HER2</i>-amplified BTC derive significant benefit from HER2-targeted therapy.</p>","PeriodicalId":14797,"journal":{"name":"JCO precision oncology","volume":"9 ","pages":"e2400718"},"PeriodicalIF":5.6000,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005869/pdf/","citationCount":"0","resultStr":"{\"title\":\"Clinicomolecular Profile and Efficacy of Human Epidermal Growth Factor Receptor 2 (HER2)-Targeted Therapy for <i>HER2</i>-Amplified Advanced Biliary Tract Cancer.\",\"authors\":\"Kanae Inoue, Yoshiaki Nakamura, Bennett Caughey, Binbin Zheng-Lin, Makoto Ueno, Masayuki Furukawa, Yasuyuki Kawamoto, Shinji Itoh, Kumiko Umemoto, Kentaro Sudo, Taroh Satoh, Nobumasa Mizuno, Takeshi Kajiwara, Takao Fujisawa, Hideaki Bando, Takayuki Yoshino, John H Strickler, Chigusa Morizane, Tanios Bekaii-Saab, Masafumi Ikeda\",\"doi\":\"10.1200/PO-24-00718\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>This study aimed to investigate the clinicomolecular profiles and the efficacy of human epidermal growth factor receptor 2 (HER2)-targeted therapy in <i>HER2</i>-amplified biliary tract cancer (BTC).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>Of the 439 patients in the exploratory cohort, 43 (10%) had <i>HER2</i> amplification. The frequencies of coalterations were higher in patients with <i>HER2</i> amplification versus patients without <i>HER2</i> amplification including <i>HER2</i> mutations (26% <i>v</i> 5%, <i>P</i> < .001), <i>TP53</i> mutations (84% <i>v</i> 61%, <i>P</i> = .003), and <i>BRAF</i> amplification (9% <i>v</i> 2%, <i>P</i> = .030). There were no <i>KRAS</i> mutations identified in patients with <i>HER2-</i>amplified BTC. No significant difference in overall survival (OS) was observed between patients with and without <i>HER2</i> amplification (median, 17.7 <i>v</i> 16.9 months; hazard ratio [HR], 0.95 [95% CI, 0.65 to 1.40]). Of the 60 patients with <i>HER2</i>-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 <i>v</i> 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]; <i>P</i> < .001).</p><p><strong>Conclusion: </strong><i>HER2</i> amplification was found in 10% of advanced BTC and was not identified as an independent prognostic factor for OS. Patients with <i>HER2</i>-amplified BTC derive significant benefit from HER2-targeted therapy.</p>\",\"PeriodicalId\":14797,\"journal\":{\"name\":\"JCO precision oncology\",\"volume\":\"9 \",\"pages\":\"e2400718\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2025-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005869/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JCO precision oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/PO-24-00718\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/4/10 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCO precision oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/PO-24-00718","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/10 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的：探讨人表皮生长因子受体2 （HER2）靶向治疗胆道癌（BTC）的临床分子特征及疗效。方法：本研究是一项国际合作，使用了来自日本前瞻性SCRUM-Japan GOZILA和MONSTAR-SCREEN以及美国回顾性综述的综合数据；已接受全身治疗的晚期BTC患者纳入研究。临床分子谱在探索性队列中进行评估，而her2靶向治疗的疗效在生物标志物选择队列中进行评估。结果：在探索性队列的439例患者中，43例（10%）有HER2扩增。HER2扩增患者的共变频率高于无HER2扩增患者，包括HER2突变（26% vs 5%, P < 0.001）、TP53突变（84% vs 61%, P = 0.003）和BRAF扩增（9% vs 2%, P = 0.030）。在her2扩增的BTC患者中未发现KRAS突变。HER2扩增患者和未扩增患者的总生存期（OS）无显著差异(中位数，17.7个月vs 16.9个月；风险比[HR]， 0.95 [95% CI, 0.65 ~ 1.40])。在生物标志物选择队列中的60例her2扩增BTC患者中（43例来自日本，17例来自美国），接受her2靶向治疗的29例患者的OS明显长于未接受her2靶向治疗的患者(中位数，24.3个月vs 12.1个月；HR, 0.39 [95% CI, 0.23 ~ 0.82])。多因素分析表明，her2靶向治疗是OS的独立预后因素(HR, 0.29 [95% CI， 0.14至0.58]；P < 0.001)。结论：在10%的晚期BTC中发现HER2扩增，但未被确定为OS的独立预后因素。her2扩增BTC患者从her2靶向治疗中获益显著。
Clinicomolecular Profile and Efficacy of Human Epidermal Growth Factor Receptor 2 (HER2)-Targeted Therapy for HER2-Amplified Advanced Biliary Tract Cancer.
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.
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