3126 - Efficacy and Safety of PD-1 Inhibitors and Targeted Drugs Combined with Radiotherapy in First-Line Treatment of Oligometastatic Hepatocellular Carcinoma

K. Zhu¹, J. Liu², X. Dou¹, X. Zhang¹, L. Xu¹, P. Shi², F. Shi¹, and J. Yue¹; ¹Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, ²Shandong Cancer Hospital affiliated to Shandong First Medical University, Jinan, Shandong, China

Purpose/Objective(s): Targeted therapy combined with immuno-therapy is the most important treatment for unresectable oligometastatic hepatocellular carcinoma (HCC), but it does not show a better therapeutic effect. Radiotherapy combined with immunotherapy produces a systematic, immune-mediated systemic anti-tumor response that helps the immune system fight tumors through a variety of mechanisms. The purpose of this study is to evaluate the efficacy and safety of targeted therapy combined with immunotherapy and radiotherapy in the treatment of unresectable oligometastatic hepatocellular carcinoma. Materials/

Methods: A single-armphase II trial was conducted with oligometastatic stage C (BCLC) hepatocellular carcinoma (HCC) whose liver function Child-Pugh score was less than B7 (clinical trial registration ethics number: ChiCTR2100049735). The metastatic foci (measurable lesions) were treated with hypofractionated radiotherapy with BED = 80 Gy for 5-10 fractions. PD-1 antibody (Carrellizumab) and VEGFR-2 target inhibitors (lamvatinib) were given simultaneously until the disease progressed. The primary endpoints are overall survival and safety. Meanwhile we collected patients with the only targeted therapy combined with immunotherapy (i.e.without radiotherapy) as the control arm to match our experimental arm based on age, sex, BCLC staging and Child pugh grade.
Results: A total of 38 eligible patients were enrolled in this clinical trial from January 2020 to December 2022, and 8 patients with loss of follow-up and treatment interruption were excluded. At the same time, 30 patients with matched oligometastatic HCC without radiotherapy in the same period were collected asthe control group. The results showed that among the 30 patients in the experimental group, the ORR was 70.00%, and the 6-month PFS rate was 57.13%, while in the 30 patients in the control group, the ORR reached 56.67%, the median of PFS was 3.5 months, and the 6-month PFS rate was 39.14%. To the follow-up time, there was no treatment-related death in both groups. The main serious side effects related to treatment were diarrhea, and 1 patient in the control group stopped taking drugs because of severe diarrhea. The common side effects in the test and control group were fatigue (15.00% vs.10.00%), abnormal liver function (36.67% vs.33.34%), increased bilirubin (13.33% vs.16.67%), thrombocytopenia (16.67% vs.13.33%) and leukopenia (10.00% vs.13.33%). Compared with the control group, the side effects were not increased and the tolerance was well.
Conclusion: The targeted therapy combined with immunotherapy and radiotherapy showed promising in the treatment of oligometastatic hepatocellular carcinoma with acceptable toxicities. However, p<span>rospective Randomized Controlled Study is warranted.