TACE Combined With Tislelizumab, Lenvatinib, and Carvedilol for Unresectable HCC With Cirrhotic Portal Hypertension

In China, the majority of hepatocellular carcinoma (HCC) cases stem from chronic hepatitis B virus (HBV) infection and subsequent cirrhosis, with patients often presenting at the decompensated stage complicated by clinically significant portal hypertension (CSPH). CSPH not only limits treatment options and worsens prognosis but also leads to the frequent exclusion of such patients from pivotal clinical trials, resulting in a lack of high-level evidence for their management. Carvedilol, a non-selective beta-blocker, is a first-line therapy for portal hypertension. Emerging evidence suggests that this drug class may also modulate the tumor microenvironment and enhance the efficacy of immune checkpoint inhibitors. To address this unmet need, this study aims to explore a novel quadruple-therapy strategy (TACE + tislelizumab + lenvatinib + carvedilol) for the treatment of unresectable HCC with concurrent cirrhotic portal hypertension. The rationale is twofold: while controlling portal hypertension and safeguarding treatment safety, carvedilol may also potentiate immunotherapy by modulating adrenergic signaling, thereby achieving dual benefits of "liver protection" and "anti-cancer" synergy. Utilizing an efficient Simon's two-stage design, this study will conduct a preliminary assessment of the regimen's efficacy and safety with minimal risk, providing essential data to inform future confirmatory research.

Sex

All

Minimum age

18 Years

Maximum age

75 Years

Inclusion Criteria:

* Aged 18-75 years.
* At least one radiologically measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (tumor lesion long axis ≥10 mm on CT scan).
* Newly diagnosed hepatocellular carcinoma without any prior treatment for HCC.
* Child-Pugh liver function score ≤ 7.
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1.
* Absence of severe organic diseases affecting major organs (e.g., heart, lung, brain).
* Compensated cirrhosis with clinically significant portal hypertension (meeting any one of the following criteria):

  1. Imaging evidence (ultrasound, CT, or MRI) of portosystemic collateral circulation.
  2. Endoscopic evidence of esophageal or gastric varices.
  3. Liver stiffness measurement (LSM) \>25 kPa; or LSM 20-25 kPa with platelet count \<150×10⁹/L; or LSM 15-20 kPa with platelet count \<110×10⁹/L.

Exclusion Criteria:

* Decompensated cirrhosis.
* Concurrent other malignancies or recurrent HCC.
* Any active, known, or suspected autoimmune disease.
* History of allergy to any component of PD-1 inhibitors, lenvatinib, or carvedilol.
* Severe concurrent medical conditions, including asthma, significant cardiac conduction block, and sinus bradycardia.
* Known human immunodeficiency virus (HIV) infection; or active hepatitis (e.g., hepatitis B/C virus infection).
* Presence of tumor thrombus in the inferior vena cava, hepatic vein, or main portal vein.