{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T16:58:48Z","timestamp":1785257928312,"version":"3.55.0"},"reference-count":19,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver Cancer"],"abstract":"<jats:p>Introduction: In CheckMate-9DW, the suboptimal early tumor control of nivolumab-ipilimumab resulted in higher early mortality compared with the sorafenib\/lenvatinib arm during the first 12 months. We evaluated whether adding lenvatinib to nivolumab-ipilimumab (NIL) improves outcomes versus nivolumab-ipilimumab (NI). Methods: Patients with unresectable HCC treated with NI with or without lenvatinib were retrospectively analyzed. Responses were evaluated by RECIST v1.1, survival outcomes by Kaplan-Meier and inverse probability of treatment weighting (IPTW) adjustment, and multiple sensitivity analyses. Liver function changes were evaluated using the albumin\u2013bilirubin (ALBI) score. Results: Among 104 patients, 82 received NI and 22 received NIL. The NIL group demonstrated a higher disease control rate than the NI group (81.8% vs. 39.0%; p &lt; 0.01), with similar duration of response (21.4 vs. 21.8 months). Median progression-free survival (PFS) was longer with NIL (10.2 vs. 3.2 months), but not for overall survival (OS). In the first-line setting, NIL showed a trend toward longer PFS and fewer early deaths within 12 months. After IPTW adjustment and sensitivity analyses, the NIL regimen consistently demonstrated improved PFS (HR 0.44; p &lt; 0.01) without a statistically significant OS benefit. Hypertension, proteinuria and stomatitis were more frequent in the NIL group, while ALBI scores remained stable. Development of immune-related adverse events was associated with improved outcomes. Conclusion: This real-world study provides proof-of-concept evidence that incorporating a VEGF inhibitor into dual ICIs therapy is associated with improved tumor control and prolonged PFS, with a potential reduction in early mortality. Prospective studies are warranted to confirm these findings.<\/jats:p>","DOI":"10.1159\/000552861","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T16:01:05Z","timestamp":1781020865000},"page":"1-14","source":"Crossref","is-referenced-by-count":0,"title":["Lenvatinib Added to Nivolumab and Ipilimumab Improves Tumor Control and Progression-Free Survival in Unresectable Hepatocellular Carcinoma"],"prefix":"10.1159","author":[{"given":"Kuan-Chang","family":"Lai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-An","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9038-3070","authenticated-orcid":false,"given":"Hao-Jan","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9436-5400","authenticated-orcid":false,"given":"San-Chi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1915745"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2100070"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)00403-9"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(24)00679-X"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212851"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-002435"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1159\/000540801"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1186\/2045-824X-6-18"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30207-1"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(23)00469-2"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1159\/000546185"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.2217\/imt.15.126"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-019-0974-6"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32023"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-022-01248-0"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2024.14445"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1159\/000502095"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10019"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.15727"}],"container-title":["Liver Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000552861","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T16:01:13Z","timestamp":1785254473000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000552861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":19,"URL":"https:\/\/doi.org\/10.1159\/000552861","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.32586525","asserted-by":"subject"}]},"ISSN":["2235-1795","1664-5553"],"issn-type":[{"value":"2235-1795","type":"print"},{"value":"1664-5553","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,9]]}}}