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Karger AG","issue":"3","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncology"],"abstract":"<jats:p>Introduction: In recent years, the therapeutic scenario of metastatic biliary tract cancers (BTCs) beyond first-line has profoundly changed owing to target therapies. human epidermal growth factor receptor-2 (HER2) represents a promising molecular target that is frequently altered in BTC. The present meta-analyses aimed to describe the response rates and survival outcomes in patients with HER2-positive locally advanced\/metastatic BTC treated with anti-HER2 therapies. Moreover, the study is intended to provide an update on the evolving therapeutic scenario of HER2-overexpressed BTC. Methods: We performed a systematic review of the literature to identify clinical trials investigating any regimen comprising a HER2-targeted therapy for metastatic BTC, and we conducted three subsequent meta-analyses on second-line phase II trials. The first one was performed to compare the group of HER2 3+ versus the group of HER2 2+ BTC patients for objective response rate (ORR). The second one compared patients according to the tumor location (gallbladder carcinoma [GBC] or extrahepatic cholangiocarcinoma [eCCA] versus intrahepatic cholangiocarcinoma [iCCA]) for ORR. The third one evaluated the overall outcomes in terms of overall survival (OS) and progression-free survival (PFS). Results: Patients with advanced BTC and HER2 3+ had better ORR compared to HER2 2+, with a 3.7-fold higher probability of experiencing objective responses (HR 3.70, 95% CI, 1.34\u201310.25, p = 0.0119). Likewise, patients with GBC or eCCA had a 2.74-fold higher probability of experiencing an objective response compared to patients with iCCA (HR 2.74, 95% CI, 1.12\u20136.73, p = 0.0275). The weighted pooled analysis of trials with anti-HER2 agents in second line or beyond revealed an mPFS of 4.9 months (95% CI, 4.2\u20135.6), while mOS was 10.8 months (95% CI, 9.0\u201312.8). Conclusions: Our meta-analyses have revealed improved efficacy in patients with HER2 3+ metastatic BTC and in patients with GBC or eCCA treated with anti-HER2 therapies, with a considerable mPFS and mOS in the overall population of the phase II trials analyzed. Further studies are paramount to confirm our preliminary results.<\/jats:p>","DOI":"10.1159\/000545308","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T12:02:01Z","timestamp":1748260921000},"page":"306-318","source":"Crossref","is-referenced-by-count":1,"title":["Anti-Human Epidermal Growth Factor Receptor-2 Therapies in Biliary Tract Cancers: A Meta-Analysis on Disease Location, Human Epidermal Growth Factor Receptor-2 Status, and Survival Outcomes"],"prefix":"10.1159","volume":"104","author":[{"given":"Silvia","family":"Camera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Rimini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Foti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Lo 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