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

Abstract

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.

PD-1 inhibitors plus anti-angiogenic therapy with or without intensity-modulated radiotherapy for advanced hepatocellular carcinoma: A propensity score matching study

“…Abulimiti et al (8) confirmed that IMRT plus sorafenib can improve the prognosis of advanced HCC, for which the mOS was observed to be 11.4 months and the mPFS was 6 months. Additionally, patients with advanced HCC who received IMRT in combination with apatinib had an mPFS of 7.8 months and an ORR of 15% (9). Radiotherapy can not only promote the generation and infiltration of T cells but also stimulate systemic anti-tumor immunity to control metastatic lesions, causing the "abscopal effect" (10).…”

Portal vein tumor thrombus radiotherapy improves the outcomes of immunotherapy plus bevacizumab in hepatocellular carcinoma: A multicenter real-world research of southwest China

“…In addition, study [17] have pointed out that the mPFS of advanced HCC patients treated with IMRT combined with apatinib was 7.8 months and the ORR is 15%. All the studies mentioned above have indicated that radiotherapy had a synergistic effect on systemic antitumor therapy.…”

Portal vein tumour thrombosis radiotherapy improves the treatment outcomes of immunotherapy plus bevacizumab in hepatocellular carcinoma: a multicentre real-world analysis with propensity score matching

“…confirmed that radiotherapy combined with sorafenib improved the survival of patients with HCC, with a median OS of 11.4 months and a median PFS of 6 months ( 15 ). Furthermore, another study ( 16 ) indicated that the mPFS of patients with advanced HCC treated with IMRT combined with apatinib was 7.8 months and the ORR was 15%. All the studies mentioned above indicate that radiotherapy has a synergistic effect on systemic anti-tumour therapy.…”