Hepatic Arterial Infusion Chemotherapy Combined With Lenvatinib and PD-1 Inhibitors for Advanced Hepatocellular Carcinoma With Macrovascular or Biliary Invasion: A Multicenter, Controlled Real-World Study
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- OS
研究概览
简要总结
The combination of HAIC with systemic therapy can provide superior efficacy compared to systemic therapy alone or local therapy alone for patients with advanced HCC complicated by vascular invasion, regardless of whether they have extrahepatic metastasis, with overall manageable safety. Currently, guidelines have recommended HAIC for HCC patients with unresectable primary tumors, PVTT type I/II/III/IV, and Child-Pugh A liver function, and recognize that its combination with sorafenib for patients with PVTT has superior efficacy compared to sorafenib monotherapy. However, more evidence is still needed regarding the efficacy of HAIC combined with lenvatinib and PD-1 inhibitors for patients with major vascular invasion (including PVTT/HVTT/IVCTT, etc.) and bile duct invasion. This study aims to further validate the efficacy and safety of lenvatinib and PD-1 inhibitors ± HAIC for HCC patients with major vascular invasion (including PVTT/HVTT/IVCTT, etc.) and bile duct invasion through larger sample size multicenter real-world data, with the goal of providing new evidence-based guidance for HCC treatment in clinical practice. This study is to evaluate the efficacy and safety of HAIC combined with lenvatinib and PD-1 inhibitors versus lenvatinib combined with PD-1 inhibitors in the first-line treatment of advanced hepatocellular carcinoma with major vascular or biliary invasion
详细描述
Primary liver cancer is one of the most common malignancies worldwide, with approximately 75%-85% being hepatocellular carcinoma (HCC). According to national cancer incidence and mortality statistics released by the National Cancer Center, there were 367,700 new cases of liver cancer in China in 2022, ranking fourth in cancer incidence; deaths reached 316,500, ranking second in cancer mortality.
Most HCC patients are diagnosed at intermediate to advanced stages and are not suitable for curative treatments, including surgical resection, ablation, or transplantation. Among them, a considerable proportion of patients have major vascular or biliary tumor thrombi, resulting in poor overall survival prognosis. Based on biological behavior and anatomical features, HCC most commonly invades the portal vein, leading to portal vein tumor thrombus (PVTT), with an incidence of approximately 44%-62.2%. Once PVTT occurs, patients can rapidly develop intrahepatic and extrahepatic metastases, portal hypertension, jaundice, ascites, etc., with a natural overall survival (OS) of only 2.7-4 months. Additionally, HCC can also involve the hepatic veins, inferior vena cava, and bile ducts. Patients with such vascular invasion likewise have a poor prognosis, frequently developing life-threatening complications such as hepatic failure or tumor thrombus embolization within a short period. The median natural OS is approximately 3 months.
In recent years, systemic therapy for advanced HCC has made substantial progress. Representative regimens including targeted therapies (e.g., lenvatinib), combinations of targeted therapy with immunotherapy, and dual immunotherapy have significantly improved patient outcomes. However, even with systemic therapy, patients with HCC complicated by PVTT, hepatic vein tumor thrombus (HVTT), inferior vena cava tumor thrombus (IVCTT), or bile duct tumor thrombus continue to have poor prognoses. Accordingly, identifying effective first-line therapeutic strategies for advanced HCC with major vascular or biliary tumor thrombi is of great clinical importance.
1.1 Current Status of Systemic Therapy for Advanced HCC For patients with vascular invasion, such as PVTT, HVTT, or IVCTT, international practice, following the Barcelona Clinic Liver Cancer (BCLC) staging system, generally classifies these cases as advanced stage (BCLC stage C) and recommends systemic therapy as the first-line treatment. China Liver Cancer Staging (CNLC) defines HCC with imaging-visible tumor thrombus but without extrahepatic metastasis as CNLC stage IIIa, recommending more comprehensive treatment strategies including systemic therapy ± TACE, surgical resection, or radiotherapy; once extrahepatic metastasis occurs, it is classified as CNLC stage IIIb, with corresponding recommended regimens being systemic therapy, TACE, or radiotherapy.
Currently, for advanced HCC with vascular invasion and/or extrahepatic metastasis, first-line systemic antitumor therapy includes tyrosine kinase inhibitors (TKIs) such as sorafenib, lenvatinib, and donafenib, immune checkpoint inhibitors (ICIs) such as tislelizumab, and immune combination regimens such as atezolizumab + bevacizumab, sintilimab + bevacizumab biosimilar, and apatinib + camrelizumab.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18-80 years, both genders;
- •Diagnosed with hepatocellular carcinoma according to the Primary Liver Cancer Diagnosis and Treatment Guidelines (2019 edition) or pathological diagnosis;
- •BCLC stage C with portal vein/hepatic vein/inferior vena cava/bile duct invasion, with or without extrahepatic metastasis;
- •At least one measurable intrahepatic lesion according to RECIST 1.1 criteria;
- •Received first-line lenvatinib + PD-1 inhibitor combination therapy or HAIC + lenvatinib + PD-1 inhibitor combination therapy between January 2020 to June 2024;
- •ECOG PS score 0-1;
- •Child-Pugh score: Class A or B (≤7); ALBI score: Grade 1-2.
排除标准
- •Previous systemic therapy for HCC (including immune checkpoint inhibitors, tyrosine kinase inhibitors, anti-VEGF antibodies, etc.) and hepatic arterial chemotherapy;
- •Received radiotherapy and other local treatments besides HAIC during treatment;
- •Received other antitumor drug therapy during treatment;
- •Previously diagnosed with fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, or other components by histology/cytology;
- •Previously diagnosed with any other malignancy, except for basal cell or squamous cell skin cancer or cervical carcinoma in situ that has been curatively treated;
- •Incomplete outcome data or missing key baseline characteristic data.
研究组 & 干预措施
HAIC-Lenva-PD1
Received HAIC combined with Lenvatinib and PD-1 inhibitor treatment
干预措施: Lenvatinib (Drug)
Lenva-PD1
Received Lenvatinib and PD-1 inhibitor treatment
干预措施: Lenvatinib 1 (Drug)
HAIC-Lenva-PD1
Received HAIC combined with Lenvatinib and PD-1 inhibitor treatment
干预措施: PD-1 Inhibitors (Drug)
Lenva-PD1
Received Lenvatinib and PD-1 inhibitor treatment
干预措施: PD-1 inhibitors 1 (Drug)
HAIC-Lenva-PD1
Received HAIC combined with Lenvatinib and PD-1 inhibitor treatment
干预措施: HAIC (Procedure)
结局指标
主要结局
OS
时间窗: From date of treatment beginning until the date of death from any cause, assessed up to 36 months.
The time from treatment initiation to death due to any cause
次要结局
- PFS(From date of treatment beginning until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.)
- TTP(From date of treatment beginning until the date of first documented progression, assessed up to 36 months.)
- ORR(From date of treatment beginning until the date of first documented progression disease, up to 36 months.)
- DCR(From date of treatment beginning until the date of first documented progression disease, up to 36 months.)
- Number of patients with treatment-related adverse events(From date of treatment beginning until the date of study treatment completion, up to 36 months.)