An exploratory clinical trial of apatinib combined with intensity‐modulated radiation therapy for patients with unresectable hepatocellular carcinoma

PURPOSE: To evaluate the clinical efficacy and safety of apatinib combined with intensity‐modulated radiation therapy (IMRT) in patients with unresectable hepatocellular carcinoma (uHCC). MATERIALS AND METHODS: Open‐label, single‐arm, exploratory clinical trial of apatinib combined with IMRT for uHCC patients. Patients aged 18–75 years with adequate hematological, liver, and renal functions and Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were enrolled in this study from March 2017 to September 2020. Patients were received IMRT (biological effective dose: 46–60 Gy) and continuous apatinib (250–500 mg/day) oral administration until HCC progression or unacceptable toxic effects. The endpoints included progression‐free survival (PFS), overall survival (OS), disease control rate (DCR), objective response rate (ORR), and safety. The trial registration number is ChiCTR‐OPC‐17011890. RESULTS: A total of 33 patients have taken part in the study. The median age was 58 years old (range 32–77), 27 (81.9%) patients were ECOG PS 0–1, and 28 (84.9%) patients were male. In addition, 25 (75.7%) patients suffered from hepatitis B, 32 cases (97.0%) were in Barcelona Clinic Liver Cancer (BCLC) Stages B–C, and eight (24.2%) had portal vein involvement. Moreover, 12 (36.4%) and 21 (63.6%) patients received apatinib as first‐line and second or later‐line therapy, respectively. The average follow‐up was 11.4 months, the median PFS was 7.8 months (95% confidence interval: 3.9–11.7). The OS rates at 6 and 12 months were 96.7% and 66.2%. The ORR and DCR were 15.1% and 81.8%, respectively. Hepatic toxicity was the most common treatment‐related adverse events in Grades 3–4 (12.1%). No radiation‐induced liver disease and Grade 5 toxicity were recorded. CONCLUSION: Apatinib combined with IMRT is a safe and effective method to improve PFS and DCR and has good anti‐tumor activity in patients with uHCC.