[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-443304-105":59,"doc-detail-443304-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","navigating-second-line-therapy-after-immunotherapy-in-advanced-hcc","Navigating second-line therapy after immunotherapy in advanced HCC","","Systemic treatment options for hepatocellular carcinoma have expanded rapidly, yet most progress has concentrated on first-line strategies, leaving uncertainty about optimal sequencing after progression. Evidence for second-line and later therapy derives mainly from post hoc analyses, real-world data, and limited phase II prospective studies, requiring integration with patient-specific factors such as prior response, liver function, and performance status. This review synthesizes current evidence and discusses emerging approaches including immunotherapy continuation and novel targeted concepts to refine treatment pathways for advanced HCC.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/navigating-second-line-therapy-after-immunotherapy-in-advanced-hcc/443304/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/navigating-second-line-therapy-after-immunotherapy-in-advanced-hcc/443304.png","ImageObject",300,407,{"name":92,"@type":93},"Liam","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is treatment sequencing difficult after immunotherapy in advanced HCC?","Question",{"text":112,"@type":113},"Clinical advances have focused largely on first-line strategies, while comprehensive head-to-head data for the best second-line sequence are still limited. Most guidance comes from post hoc analyses and select prospective studies.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What sources of evidence guide second-line therapy decisions?",{"text":117,"@type":113},"Evidence mainly comes from post hoc analyses, real-world data, and selected phase II prospective studies. Clinicians also weigh these findings alongside individual patient factors.",{"name":119,"@type":110,"acceptedAnswer":120},"Which patient factors influence choosing second-line treatment?",{"text":121,"@type":113},"Decisions integrate prior treatment response, liver function, and performance status. Regulatory and accessibility constraints may also affect available options.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},443304,1791289795,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},8796095461564,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Review  \nNavigating second-line therapy after immunotherapy  \nin advanced HCCq  \nArndt Vogel1 ,2 ,3 ,* ,†, Anna Saborowski1 ,†, Lorenza Rimassa4 ,5 ,‡, Anthony El-Khoueiry6 ,* ,‡  \nSummary  \nIn recent years, systemic treatment options for hepatocellular carcinoma have expanded significantly, with pivotal phase III trials reporting unprecedented improvements in survival and response outcomes. However, these advances have largely focused on first-line strategies, challenging existing treatment sequences and raising questions about the optimal therapeutic approach following disease progression. Several therapeutic options are available in second and later lines — including immunotherapies, tyrosine kinase inhibitors, and local therapies — but so far comprehensive head-to-head comparisons to establish the ideal treatment sequence are lacking. Consequently, most evidence guiding second-line therapy has been derived from post hoc analyses, real-world data, and select prospective studies, primarily based on phase II designs. In clinical practice, treatment decisions integrate this evolving evidence base with patient-specific factors such as prior treatment response, liver function, and performance status, often within the constraints of regulatory and accessibility considerations. Ongoing research is investigating novel approaches, including the continuation of immunotherapy following progression, the application of CAR T cells, and targeted treatments against specific markers like fibroblast growth factor 19 and glypican-3 . This review summarises the current evidence for second-line and subsequent therapies, explores key considerations in treatment sequencing, and highlights emerging strategies that may further refine the therapeutic landscape for hepatocellular carcinoma.  \n© 2025 The Author(s) . Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL) . This is an open access article under the CC BY license ([http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/)).  \nIntroduction  \nHepatocellular carcinoma (HCC) is the most common primary liver cancer and often presents on a background of cirrhosis.1–4 The management of HCC necessitates a multidisciplinary approach, with treatment decisions influenced by an array offactors, including liver function, tumour-specific characteristics and the patient’s performance status. The Barcelona Clinic Liver Cancer staging system is the most commonly employed framework for classifying HCC based on these factors, and it is endorsed by most Western clinical guidelines.2–4 Treatment modalities for HCC are categorised into potentially curative options – such as liver transplantation, surgical resection orablation – and palliative approaches, which include radiation, embolisation, and systemic therapy (Fig. 1) .  \nSystemic therapy is the preferred treatment modality for patients with advanced-stage disease and in those with intermediate-stage disease who do not qualify for, or have progressed on, local therapies. Survival of patients treated with systemic agents has significantly improved over time and, with the approval of nine treatment regimens by the FDA and EMA, sequential therapy can now be routinely considered for patients with advanced HCC. The selection of systemic  \ntherapy for an individual patient will be influenced by several factors including efficacy and toxicity, and the presence of contraindications or predictive factors. In general patients should have Child-Pugh A liver disease and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1, consistent with the population in which the evidence base was generated. For most patients, combination therapy including a programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitor represents the first-line treatment of choice. According to data from the pivotal trials, approximately 50% to 60% of patients with advanced HCC are able to proceed ","cbCait7H0tdMFn65","https://ap.wps.com/l/cbCait7H0tdMFn65","pdf",944439,"English","# Summary\n# Introduction\n## Keypoints","[{\"question\":\"Why is treatment sequencing difficult after immunotherapy in advanced HCC?\",\"answer\":\"Clinical advances have focused largely on first-line strategies, while comprehensive head-to-head data for the best second-line sequence are still limited. Most guidance comes from post hoc analyses and select prospective studies.\"},{\"question\":\"What sources of evidence guide second-line therapy decisions?\",\"answer\":\"Evidence mainly comes from post hoc analyses, real-world data, and selected phase II prospective studies. Clinicians also weigh these findings alongside individual patient factors.\"},{\"question\":\"Which patient factors influence choosing second-line treatment?\",\"answer\":\"Decisions integrate prior treatment response, liver function, and performance status. Regulatory and accessibility constraints may also affect available options.\"}]","Navigating second-line therapy after immunotherapy in advanced HCC | PDF",1790703565,25]