A Phase 2 Trial of Apatinib Combined With Intensity Modulated Radiation Therapy for Patients With Unresectable Hepatocellular Carcinoma.

Purpose/Objective(s) To estimate the clinical outcomes and safety for patients with unresectable advanced hepatocellular carcinoma (HCC) treated with apatinib in combination with intensity modulated radiation therapy (IMRT). Materials/Methods This study was an open-label, single-arm, phase 2 clinical trial of apatinib combined with IMRT for treatment of patients with unresectable advanced HCC. Patients aged between 18 and 75 years with adequate hematologic, liver, and renal functions, and ECOG performance status of 1 or less were included in the study between March 2017 and September 2020. Patients received IMRT (BED: 46-60Gy), and continuous apatinib (250-500 mg/d) orally until disease progression or unacceptable toxic effects. The primary end point was progression-free survival (PFS), the secondary end points included overall survival (OS), disease control rate (DCR), objective response rate (ORR) and safety. The data were analyzed for this report with cutoff on February 1, 2021. Results A total of 46 patients were screened and 33 were enrolled in this study. The cohort had a median age of 56.7 years (range 32-77), 31 (93.9%) were ECOG PS 0-1, 28 (84.85%) were men. 25 (75.76%) patients had hepatitis B, 32 (96.7%) were BCLC stage B-C, 31 (93.9%) were Child-Pugh A-B, and 8 (24.2%) had portal vein involvement. Receiving first-line and second- or later-line treatment were 21 (63.6%) and 12 (36.4%), respectively. At a median follow-up of 11.6 months, the median PFS was 7.80 months (95% confidence interval:3.92-11.69). The 6-month and 12-month overall survival rates were 96.7% and 66.2%, respectively. According to Response Evaluation Criteria in Solid Tumors Version 1.1, the ORR and DCR were 15% and 82%, respectively. There were 15 (15.2%) grade 3-4 treatment-related adverse events including neutropenia, thrombocytopenia, hypertension, proteinuria and hand and foot syndrome. There were no treatment-related deaths. Conclusion Apatinib in combination with IMRT was safe and effective in improving PFS and DCR, and suggested an encouraging anti-tumor activity in patients with unresectable advanced HCC.