Lenvatinib Plus Bevacizumab and PD-1 Inhibition Versus Bevacizumab Plus PD-1 Inhibition After Progression on Bevacizumab Plus Sintilimab in Unresectable Hepatocellular Carcinoma: A Prospective, Randomized, Two-Cohort, Phase II Study

This retrospective study looks at patients with unresectable hepatocellular carcinoma whose cancer progressed after treatment with bevacizumab plus sintilimab. The study compares two treatment approaches used after progression: lenvatinib plus bevacizumab and a PD-1 inhibitor, versus bevacizumab plus a PD-1 inhibitor alone. We will compare how well these treatments control the cancer, how long patients remain free from disease progression, overall survival, and treatment-related side effects. All information will be collected from existing medical records. No additional tests, treatments, or visits are required because of this study. Patient information will be de-identified and kept confidential. The goal of this study is to better understand whether adding lenvatinib may improve outcomes after bevacizumab plus sintilimab treatment has stopped working, and to provide evidence that may help guide future treatment decisions.

Inclusion Criteria: 1. Diagnosed with hepatocellular carcinoma (HCC) based on histological or clinical diagnostic criteria; 2. Classified as unresectable HCC following multidisciplinary assessment; 3. Presence of at least one tumor lesion measurable according to EASL criteria; 4. Patients aged ≥18 years and ≤75 years receiving first-line treatment; 5. Child-Pugh liver function class A/B, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score 0-2; 6. Disease progression confirmed by CT/MRI and evaluated according to modified RECIST (mRECIST)/RECIST v1.1 criteria after ≥2 cycles of first-line therapy with bevacizumab (15 mg/kg intravenous infusion, once every 3 weeks) combined with sintilimab (200 mg intravenous infusion, once every 3 weeks); 7. Received ≥2 cycles of post-progression treatment with bevacizumab plus sintilimab, lenvatinib, or regorafenib combined with PD-1 inhibitors; 8. Laboratory parameters: hemoglobin(Hb) ≥8.5 g/dL, white blood cell (WBC) count \>2000/mm³, platelet (PLT) count ≥75,000/mm³, absolute neutrophil count (ANC) \>1500/mm³, total bilirubin ≤30 μmol/L, serum albumin ≥30 g/L, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 times the upper limit of normal (ULN), serum creatinine ≤1.5 times ULN, international normalized ratio (INR) ≤1.5, prothrombin time (PT) ≤18 seconds; 9. Availability of complete baseline data, treatment records, and follow-up data (including imaging assessments, laboratory tests, and clinical documentation). Exclusion Criteria: 1. Life expectancy ≤2 months; 2. Presence of intrahepatic cholangiocarcinoma, mixed hepatocellular-cholangiocarcinoma, or other non-HCC malignancies; 3. Active concurrent malignancy or severe comorbid conditions; 4. First-line treatment with other anticancer therapies (chemotherapy, radiotherapy, surgery, or other interventions) concurrently; 5. Known hypersensitivity to study drugs.