{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:41:40Z","timestamp":1790775700455,"version":"4.1.0"},"reference-count":12,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver Cancer"],"published-print":{"date-parts":[[2021]]},"abstract":"<b><i>Introduction:<\/i><\/b> Atezolizumab-bevacizumab is the new standard of care for first-line treatment of advanced hepatocellular carcinoma (HCC). However, the optimal sequence of therapy after disease progression on atezolizumab-bevacizumab is unclear. <b><i>Methods:<\/i><\/b> This multinational, multicenter, and retrospective study assessed clinical outcomes of patients with advanced HCC who received subsequent systemic therapy after progression on atezolizumab-bevacizumab between July 2016 and April 2019. <b><i>Results:<\/i><\/b> Among 71 patients treated with atezolizumab-bevacizumab, a total of 49 patients who received subsequent systemic therapy were included in this analysis; the median age was 60 years (range, 37\u201380) and 73.5% were male. All patients were classified as Child-Pugh A and Barcelona-Clinic Liver Cancer stage C. Multikinase inhibitors (MKIs), including sorafenib (<i>n<\/i> = 29), lenvatinib (<i>n<\/i> = 19), and cabozantinib (<i>n<\/i> = 1), were used as second-line therapy for all patients. The objective response rate and disease control rate were 6.1 and 63.3%, respectively, in all patients. With a median follow-up duration of 11.0 months, median progression-free survival (PFS) and overall survival (OS) were 3.4 months (95% confidence interval [CI] 1.8\u20134.9) and 14.7 months (95% CI 8.1\u201321.2) in all patients. Median PFS with lenvatinib was significantly longer than that with sorafenib (6.1 vs. 2.5 months; <i>p<\/i> = 0.004), although there was no significant difference in median OS (16.6 vs. 11.2 months; <i>p<\/i> = 0.347). Treatment-related adverse events (TRAEs) of any grade and grade 3 occurred in 42 (85.7) and 8 (16.3%) of patients. Common TRAEs included hand-foot syndrome (<i>n<\/i> = 26, 53.1%), fatigue (<i>n<\/i> = 14, 28.6%), hypertension (<i>n<\/i> = 14, 28.6%), and diarrhea (<i>n<\/i> = 12, 24.5%). <b><i>Conclusion:<\/i><\/b> Second-line treatment with MKIs, mostly sorafenib and lenvatinib, showed comparable efficacy and manageable toxicities in patients with advanced HCC after disease progression on atezolizumab-bevacizumab.<\/jats:p>","DOI":"10.1159\/000512781","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T13:29:11Z","timestamp":1616506151000},"page":"107-114","source":"Crossref","is-referenced-by-count":117,"title":["Clinical Outcomes with Multikinase Inhibitors after Progression on First-Line Atezolizumab plus Bevacizumab in Patients with Advanced Hepatocellular Carcinoma: A Multinational Multicenter Retrospective Study"],"prefix":"10.1159","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1451-8455","authenticated-orcid":false,"given":"Changhoon","family":"Yoo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jwa Hoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Hee","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sook Ryun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danbi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang Mo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7336-1371","authenticated-orcid":false,"given":"Ju Hyun","family":"Shim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1544-577X","authenticated-orcid":false,"given":"Young-Suk","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7631-4124","authenticated-orcid":false,"given":"Han Chu","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joycelyn","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Tai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen Lam","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baek-Yeol","family":"Ryoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0186-y"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0708857"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30207-1"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32453-9"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1717002"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz394.029"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.01307"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30156-X"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915745"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(08)70285-7"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.59125"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.09.025"}],"container-title":["Liver Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/512781","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/512781","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T12:06:59Z","timestamp":1745410019000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000512781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021]]},"references-count":12,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,4,13]]},"published-print":{"date-parts":[[2021,4,20]]}},"URL":"https:\/\/doi.org\/10.1159\/000512781","archive":["Portico"],"relation":{},"ISSN":["2235-1795","1664-5553"],"issn-type":[{"value":"2235-1795","type":"print"},{"value":"1664-5553","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021]]}}}