{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:16:17Z","timestamp":1790864177152,"version":"4.1.0"},"reference-count":59,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"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: Transarterial chemoembolization (TACE) combined with lenvatinib has demonstrated efficacy for unresectable hepatocellular carcinoma (HCC). However, real-world evidence on the additional benefit of PD-1 inhibitors in conversion therapy remains limited. This study aimed to investigate the efficacy and safety of triple therapy (TACE, lenvatinib, and PD-1 inhibitors) versus dual therapy (TACE and lenvatinib) in conversion therapy for initially unresectable HCC. Methods: This multicenter study was conducted in 20 Chinese tertiary hospitals. Patients received either triple therapy (TLP group, n = 289) or dual therapy (TL group, n = 132). Inverse probability of treatment weighting (IPTW) was used to control for confounding. Multivariate models compared overall survival (OS) and progression-free survival (PFS). Results: From January 2019 to June 2023, 421 consecutive patients were enrolled. After IPTW adjustment, baseline characteristics were well balanced. The TLP group showed superior efficacy: objective response rate 55.1% versus 34.7% (p &lt; 0.001), complete response rate 24.9% versus 14.9% (p = 0.010), and conversion surgery rate 35.5% versus 15.7% (p &lt; 0.001). Median OS was prolonged (31.67 vs. 25.00 months; adjusted HR 0.60, 95% CI: 0.42\u20130.85, p = 0.001) and median PFS extended (16.47 vs. 12.00 months; adjusted HR 0.65, 95% CI: 0.47\u20130.93, p = 0.008). Sensitivity analyses including propensity score matching (HR 0.61), landmark analysis (HR 0.64), and time-varying covariate analysis (HR 0.58) confirmed the findings. E-value analysis (2.72) suggested unmeasured confounding alone is unlikely to explain the benefit. Treatment effects were consistent across subgroups. Grade 3\u20134 adverse events were similar (35.6% vs. 36.4%, p = 0.885), though immune-related adverse events were more frequent in the TLP group. Conclusions: Adding PD-1 inhibitors to TACE plus lenvatinib was associated with improved tumor response, prolonged survival, and higher conversion surgery rates, with an acceptable safety profile. Given the heterogeneity of PD-1 inhibitors and inherent limitations of retrospective design, these findings should be considered hypothesis generating and require verification in prospective randomized controlled trials.<\/jats:p>","DOI":"10.1159\/000552409","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T16:00:45Z","timestamp":1778083245000},"page":"1-19","source":"Crossref","is-referenced-by-count":1,"title":["Real-World Efficacy and Safety of TACE Combined with Lenvatinib and PD-1 Inhibitor in Conversion Therapy for Unresectable Hepatocellular Carcinoma (GUIDANCE007): A Multicenter Retrospective 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