Hepatic arterial infusion chemotherapy plus lenvatinib and PD-1 inhibitors as first-line treatment for hepatocellular carcinoma with high tumor burden and portal vein tumor thrombus.

4108 Background: Advanced-stage hepatocellular carcinoma (HCC) is usually associated with poor survival outcomes. Rapid tumor control usually benefits long-term outcomes, which could be hardly achieved by solely systematic targeted and immunotherapy in current guidelines. This study aimed to evaluate the efficacy of hepatic arterial infusion chemotherapy (HAIC) combined with lenvatinib and PD-1 inhibitors (HLP) as first-line treatment for HCC patients with high tumor burden and portal vein tumor thrombus (PVTT). Methods: This retrospective multicenter study screened advanced HCC patients who received HLP combination therapy as first-line treatment at ten centers from Jan 2021 to Dec 2023. The inclusion criteria included high tumor burden (up to seven criteria out), PVTT, no extra-hepatic metastasis, and liver function of Child-Pugh B7 or better. PD-1 inhibitors permitted 3 different products, including Tislelizumab. Tumor response was assessed using both RECIST 1.1 and mRECIST criteria. Survival outcomes were analyzed using Kaplan-Meier methods. The primary endpoint was overall survival (OS), while secondary endpoints comprised progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), as well as depth of response (DpR) within 3 months. Baseline time point was defined as start of any designed treatment except DpR related survival as 3 months after initial treatment. Results: A total of 94 patients were included. The median age was 53 years (range: 31-78) and 87.2% (82/94) were male. In all the patients, 58.5% (55/94) had a largest tumor diameter ≥10 cm, and 80.4% (74/92) had PVTT classified as Vp3 or Vp4. The median follow-up time was 13.3 (8.9-25.2) months, the 12-month OS rate was 75.6% (95% CI: 67.0-85.3), and the 24-month OS rate was 57.6% (95% CI: 46.9-70.7). Median PFS was 9.7 months (95% CI: 8.1-16.0), with 12- and 24-month PFS rates of 46.3% (95% CI: 37.1-57.8) and 32.1% (95% CI: 23.3-44.3), respectively. Based on RECIST 1.1 or mRECIST, the ORR was 42.6% (95% CI: 32.4-53.2) or 70.2% (95% CI: 59.9-70.2), and the DCR was 96.8% (91.0-99.3) or 100% (96.2-100), respectively. Regarding DpR within 3 months, 46.8% (44/94) of the patients had > 25% tumor diameter reduction per RECIST 1.1, while 73.4% (69/94) showed > 25% reduction per mRECIST. In subgroup analyses, DpR was significantly correlated with PFS and OS (see table), while largest tumor diameter, tumor number, and Vp classification had no correlation with survival outcomes. Conclusions: Combination of HLP as a first-line treatment for advanced HCC with high tumor burden and PVTT is promising, with high ORR and survival outcomes. DpR might be a predictor for survival. Clinical trial information: NCT06631326 . Outcomes DpR≤25% DpR>25% PFS Events/N 37/50 24/44 Median (m) 6.8 (5.4-10.9) 16.0 (11.0-NR) P 0.004 OS Events/N 24/50 12/44 Median (m) 19.2 (12.6-NR) 35.0 (24.5-NR) P 0.034