Hepatocellulcar Carcinoma
Conditions
Keywords
Bevacizumab, Sintilimab, Lenvatinib, Regorafenib, PD-1, ICIs, second-line treatment
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.
Interventions
DRUGLenvatinib
Lenvatinib, for weight ≤60 kg, 8 mg/d, po, qd; for weight \>60 kg, 12 mg/d, po, qd.
DRUGRegorafenib
Regorafenib, 160mg/d, po, qd.
DRUGPD-1 Inhibitor
PD-1 inhibitor (Sintilimab, Camrelizumab, Tislelizumab, Toripalimab, Pembrolizumab, Nivolumab), 200mg/dose, iv drip, q3w.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 6 months | OS is the length of time from the date of randomization until death from any cause. |
| Progression Free Survival (PFS) | 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
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 6 months | ORR, as determined based on tumor response according to RECIST 1.1, is defined as the proportion of all randomized subjects whose best overall response (BOR) is either a CR or PR. |
| Adverse Events | 30 days | ORR, as determined based on tumor response according to RECIST 1.1, is defined as the proportion of all randomized subjects whose best overall response (BOR) is either a CR or PR. |
Countries
China
Outcome results
None listed