Efficacy and Safety Comparison Between Intensified Therapy and Conversion Therapy For Advanced HCC After Failure of First-line

Prior treatment

• Active concurrent malignancy or severe comorbid conditions;
• First-line treatment with other anticancer therapies (chemotherapy, radiotherapy, surgery, or other interventions) concurrently;
• Clinically significant gastrointestinal bleeding within 30 days prior to enrollment;

Other illness

• Presence of intrahepatic cholangiocarcinoma, mixed hepatocellular-cholangiocarcinoma, or other non-HCC malignancies;
• Known hypersensitivity to study drugs;

Other

• Life expectancy ≤2 months;
• Pregnancy or lactation;
• Refusal to comply with study and/or follow-up procedures.

• Diagnosed with hepatocellular carcinoma (HCC) based on histological or clinical diagnostic criteria;
• Classified as unresectable HCC following multidisciplinary assessment;
• Presence of at least one tumor lesion measurable according to EASL criteria;
• Child-Pugh liver function class A/B, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score 0-2;
• 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);
• Received ≥2 cycles of post-progression treatment with bevacizumab plus sintilimab, lenvatinib, or regorafenib combined with PD-1 inhibitors;
• Age ≥18 and ≤75 years;
• Capability to comprehend the study protocol and provide written informed consent;
• 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;
• Availability of complete baseline data, treatment records, and follow-up data (including imaging assessments, laboratory tests, and clinical documentation).