Camrelizumab, Apatinib, and Radiotherapy in Locally Advanced, Unresectable Hepatocellular Carcinoma: A Phase II Study

PURPOSE: Given the underexplored combination of immune checkpoint inhibitors, tyrosine kinase inhibitors (TKI), and radiotherapy in locally advanced, unresectable hepatocellular carcinoma (HCC), this study aimed to evaluate camrelizumab (a programmed cell death protein 1 inhibitor), apatinib (a TKI), and intensity-modulated radiotherapy (IMRT) for this setting and identify potential biomarkers. PATIENTS AND METHODS: This single-arm phase II trial enrolled patients with locally advanced, unresectable HCC who were systemic treatment-naïve or refractory/intolerant to first-line targeted therapy. Patients received IMRT (50-60 Gy) to all lesions plus camrelizumab (200 mg intravenously every 3 weeks) and apatinib (250 mg orally once daily) for up to 2 years. The primary endpoint was progression-free survival (PFS); secondary endpoints included response, overall survival (OS), and safety. RESULTS: Between October 2020 and November 2024, 44 patients were enrolled. Forty patients (90.9%) had Barcelona Clinic Liver Cancer stage C disease, including macrovascular invasion in 36 (81.8%) and lymph node spread in 11 (25%) cases. The objective response rate was 84.1%. The median PFS was 13.8 months, and the median OS was not reached. The 24-month PFS rate was 38.1%, and the OS rate was 70.2%. Grade 3 to 4 treatment-related adverse events occurred in 36 patients (81.8%), the most common being thrombocytopenia (36.4%) and hypertension (29.5%). No treatment-related deaths were observed. TP53 mutation in circulating tumor DNA was associated with worse clinical outcomes. CONCLUSIONS: Camrelizumab and apatinib with radiotherapy demonstrated encouraging efficacy with manageable toxicity in locally advanced, unresectable HCC, warranting randomized trials for validation.