Phase 2 study of camrelizumab plus apatinib and radiotherapy in locally advanced, unresectable hepatocellular carcinoma

A phase 2 study at Peking University Cancer Hospital (Beijing, China) evaluated the combination of camrelizumab (PD-1 inhibitor), apatinib (TKI) and intensity-modulated radiotherapy (IMRT) for locally advanced, unresectable hepatocellular carcinoma (HCC). Forty-four patients who were systemic treatment-naïve or refractory/intolerant to first-line targeted therapy 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. Forty patients (90.9%) had BCLC stage C disease, including macrovascular invasion in 36 (81.1%) and lymph node spread in 11 (25.0%). Objective response rate was 84.1%. Median progression-free survival (PFS; primary endpoint) was 13.8 months and median overall survival (OS) was not reached; 24-months PFS rate was 38.1% and 24-months OS rate 70.2%. Grade 3-4 treatment-related adverse events occurred in 36 patients (81.8%), the most common being thrombocytopenia and hypertension. No treatment-related deaths were observed. TP53 mutation in circulating tumor DNA was associated with worse clinical outcomes. The authors conclude that the combination of camrelizumab, apatinib and IMRT demonstrated encouraging efficacy with manageable toxicity in locally advanced, unresectable HCC.