The Efficacy and Safety of PD-1 Inhibitor Combined With Lenvatinib or With Regorafenib For Advanced Hepatocellular Carcinoma After Failure of First-line Bevacizumab Plus Sintilimab: A Retrospective Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 200
- Locations
- 1
- Primary Endpoint
- Overall Survival (OS)
Study Overview
Brief Summary
There is no definitive evidence regarding the therapeutic efficacy of PD-1 inhibitors combined with tyrosine kinase inhibitors (TKIs) after disease progression following first-line treatment with bevacizumab plus sintilimab for unresectable hepatocellular carcinoma (HCC). There is insufficient evidence to support which TKI should be combined with PD-1 inhibitors as the optimal second-line treatment option after first-line therapy failure. Data on the application of lenvatinib as a second-line treatment are limited, whereas the efficacy and safety of regorafenib combined with PD-1 inhibitors have been preliminarily validated [9]. Therefore, this study aims to compare the efficacy and safety of PD-1 inhibitors combined with either lenvatinib or regorafenib after disease progression following first-line bevacizumab plus sintilimab treatment for unresectable HCC, providing evidence-based guidance for the selection of second-line treatment regimens in clinical practice.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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;
- •Patients aged ≥18 years and ≤75 years receiving first-line treatment;
- •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;
- •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).
Exclusion Criteria
- •Life expectancy ≤2 months;
- •Presence of intrahepatic cholangiocarcinoma, mixed hepatocellular-cholangiocarcinoma, or other non-HCC malignancies;
- •Active concurrent malignancy or severe comorbid conditions;
- •First-line treatment with other anticancer therapies (chemotherapy, radiotherapy, surgery, or other interventions) concurrently;
- •Known hypersensitivity to study drugs.
Arms & Interventions
LP Group
Lenvatinib, PD-1 Inhibitor
Intervention: PD-1 Inhibitor (Drug)
RP Group
Regorafenib, PD-1 Inhibitor
Intervention: PD-1 Inhibitor (Drug)
LP Group
Lenvatinib, PD-1 Inhibitor
Intervention: Lenvatinib (Drug)
RP Group
Regorafenib, PD-1 Inhibitor
Intervention: Regorafenib (Drug)
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: 6 months
OS is the length of time from the date of randomization until death from any cause.
Progression Free Survival (PFS)
Time Frame: 6 months
PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression or death due to any cause.
Secondary Outcomes
- Objective Response Rate (ORR)(6 months)
- Adverse Events(30 days)
Investigators
Shi Ming
Professor
Sun Yat-sen University