A prospective non-randomized clinical study to evaluate the efficacy of intraperitoneal PD-1 monoclonal antibody for end-stage liver cancer patients with ascites: Long-term outcomes.

Abstract

e16203 Background: Patients (pts) with primary hepatocellular carcinoma and significant malignant ascites are typically in the terminal stage of the disease (BCLC stage D or CNLC stage IV), with a life expectancy of less than three months. Current guidelines recommend best supportive care (BSC) due to the lack of clinical studies addressing this condition. Preclinical research highlights immunosuppressive cells in the peritoneal cavity. This study builds on previous case trials to assess the safety and efficacy of intraperitoneal PD-1 monoclonal antibody infusion combined with BSC. Methods: The study enrolled pts with advanced primary liver cancer (including hepatocellular carcinoma and cholangiocarcinoma), presenting with substantial malignant ascites, an ECOG PS 2-3, and a life expectancy of less than three months. After adequate drainage of the ascites, pts received intraperitoneal infusions of sintilimab, a PD-1 monoclonal antibody, at 100 mg once weekly for three consecutive weeks, with 28-day cycles. Treatment was continued until disease progression, intolerable toxicity, or death from any cause. The primary endpoint was safety, and secondary endpoints included ascites control rate, OS, and ORR. Results: From February 2021 to August 2024, 164 pts were enrolled, with 54 in the treatment group and 110 in the control group. The mean age in treatment group was 57.6 years, comprising 39 males and 12 females; 37 pts were diagnosed with hepatocellular carcinoma. and 17 with cholangiocarcinoma. In the control group, the mean age was 56 years, with 80 males and 30 females; 82 pts had hepatocellular carcinomas, and 28 had cholangiocarcinomas. Among the control group, 35 pts received intravenous PD-1 monoclonal antibody treatment. As of September 10, 2024, 39 pts in the treatment group and 103 pts in the control group had died. The median OS in the treatment group was 3.9 months (95% CI: 2.743-5.057), compared to 1.3 months (95% CI: 0.499-2.041) in the control group (p = 0.001). Among pts with ascites in the control group, those who received PD-1 therapy intravenously had a median OS of 1.3 months (95% CI: 0.492-2.048), which was shorter than the 2.0 months (95% CI: 0.736-3.204) observed in patients who only received BSC (p = 0.31). The treatment was well-tolerated, with an acceptable safety profile and good patient compliance. Conclusions: These results suggest that in terminal-stage primary liver cancer patients with ascites, intraperitoneal PD-1 monoclonal antibody administration may provide a survival benefit. Systemic immunotherapy appeared to offer no improvement and, in some cases, resulted in worse outcomes than BSC. A large, multicenter, prospective, randomized study is warranted to confirm the promising clinical efficacy observed in this single-center exploratory trial. Clinical trial information: ChiCTR2100043683 .