Target trial emulation study of transarterial chemoembolization with immunotherapy and anti-angiogenic agents in intermediate-stage HCC

The nationwide, retrospective CHANCE2202 cohort study in China employing a target trial emulation framework with a cloning-censoring-weighting approach compared transarterial chemoembolization (TACE) with immune checkpoint inhibitors (ICIs) plus VEGF inhibitors or TKIs (‘combination therapy’) versus TACE monotherapy as first-line treatment for intermediate-stage hepatocellular carcinoma (HCC). Patients receiving either combination therapy (n=308) or TACE monotherapy (n=633) between 2018 and 2022 in China were included. Co-primary outcomes were overall survival (OS) and progression-free survival (PFS), assessed using restricted mean survival time. Median OS was 32.9 months with combination therapy versus 23.0 months with TACE monotherapy (HR 0.57; 95% CI 0.43-0.70) and median PFS was 18.0 months versus 12.9 months, respectively (0.70; 0.58-0.82); the objective response rate per RECIST1.1 was 60.5% versus 44.3% (p<0.001). The safety profile of the combination was acceptable. The authors conclude that combining TACE with ICIs and angiogenic agents was associated with improved OS and PFS compared with TACE monotherapy, supporting its use as first-line treatment strategy for intermediate-stage HCC.