Ablation in Combination With Lenvatinib and Anti-PD-1 Antibodies in Patients With Early Recurrence After Radical Resection/Ablation of HCC: a Prospective, Randomized, Controlled Clinical Study
Lenvatinib is an oral multi-target receptor tyrosine kinase inhibitor (TKI) inhibitor that mainly inhibits the Endothelial growth factor receptor (VEGFR) VEGFR-1,2,3; Fibroblast growth factor receptor, FGFR) FGFR-1,2,3,4; Platelet-derived growth factor receptor (PDGFR) PDGFRα; The kinases RET and KIT, thereby inhibiting tumor cell proliferation, inducing apoptosis, and playing an anti-angiogenic role, have been approved by the FDA and CFDA as first-line treatment for patients with advanced liver cancer. lenvatinib showed longer disease progression than sorafenib (8.9 months vs. sorafenib. 3.7 months), longer progression-free survival (7.4 months vs. 3.7 months), and higher disease control rates (24.1% vs. 9.2%). Therefore, lenvatinib has obvious advantages in HCC treatment because of its strong anti-angiogenic and anti-tumor growth effects. Cindilimab is a human immunoglobulin G4 (IgG4) monoclonal antibody that specifically binds to PD-1 molecules on the surface of T cells, thereby blocking the programmed death receptor-1 (PD-1)/programmed death receptor-1 ligand (PD-L1) pathway induced by tumor immune tolerance, and reactivating the antitumor activity of lymphocytes. In summary, recurrence after radical treatment of liver cancer is an urgent clinical problem. Recurrent HCC treatment represented by resection, ablation and TACE is difficult to achieve more satisfactory efficacy. The main ablative techniques includes radiofrequency ablation, microwave ablation and cryoablation.As a local treatment for liver cancer, ablation has the risk of incomplete ablation and insufficient ablation margin, and because RFA cannot resolve micrometastases, tumor growth, invasion and metastasis occur. Therefore, ablation combined with lenvatinib and immune checkpoint inhibitors have theoretical complementary advantages, and this study intends to compare the clinical efficacy and safety of ablation combined with lenvatinib plus anti-PD-1 antibodies in the treatment of patients with early recurrent liver cancer compared with ablation alone.
• Age ≥18 years old, ≤75 years old, gender unlimited;
• primary hepatocellular carcinoma proved pathologically and clinically;
• 2 months after radical resection or ablation, imaging examination (MRI, CT plain enhanced) showed no tumor lesions, HCC recurred within 3 years after surgery, no extrahepatic metastasis;
• ECOG score 0-1;
• Recurrent liver cancer meets the Milan criteria: single tumor diameter ≤5cm or multiple tumors less than 3 with a maximum diameter ≤3cm, no major vascular invasion, no lymph node metastasis or extrahepatic metastasis;
• Child-Pugh liver function grades: A, B;
• Expected survival \> 6 months;
• Adequate organ function: ① no need for growth factors and blood components within 2 weeks prior to enrollment; (2) Cardiac function: no heart disease, coronary heart disease, cardiac function level 1-2; ③ In the first 7 days of enrollment, liver and kidney function was adequate and laboratory indicators were suitable (untreated) : HGB≧9.0g/dl, neutrophils ≧1,500/mm3, PLT≧50x109/L, serum ALB≧28g/L, TBIL\<2mg /dL, ALT, AST\< 5 times of the upper limit of normal value, Bun, Cr\< 1.5 times of the upper limit of normal value, INR\<1.7 or extended PT\<3s;
• Patients with normal blood pressure or hypertension should use antihypertensive drugs to control blood pressure within the normal range;
⁃ Diabetic patients should control fasting blood glucose ≤8mmol/L by hypoglycemic drugs;
⁃ No other serious diseases (such as autoimmune diseases, immune deficiency, organ transplantation, etc.) that conflict with the Plan;
⁃ No history of other malignant tumors;
⁃ Women of childbearing age must have a negative blood pregnancy test within seven days, and subjects of childbearing age must use appropriate contraception during the test and for six months after the test;
⁃ The patient agrees to participate in the clinical study and sign the Informed Consent.