|Year : 2019 | Volume
| Issue : 4 | Page : 741-742
Apatinib for hepatocellular carcinoma
Yang Ni, Xin Ye
Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, China
|Date of Web Publication||14-Aug-2019|
Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, Shandong Province 250021
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Ni Y, Ye X. Apatinib for hepatocellular carcinoma. J Can Res Ther 2019;15:741-2
Primary hepatocellular carcinoma (HCC) ranks the second leading cause of cancer-related deaths in men worldwide with a poor prognosis. For advanced patients, sorafenib is currently the standard therapy, which extended the overall survival (OS) by 2.8 months compared to best supportive care. However, high cost, drug resistance, and severe side effects often lead to treatment discontinuation. Apatinib (Hengrui Pharmaceutical Co., Ltd, Shanghai, China) is a novel, small-molecule, tyrosine kinase inhibitor which has higher selective inhibition of vascular endothelial growth factor receptor-2 than sorafenib, leading to suppression of tumor growth by targeting tumor angiogenesis. Apatinib was approved in China in 2014 as a subsequent-line treatment for patients with advanced gastric cancer. In addition, accumulating studies showed its potential antitumor activity across a broad range of advanced solid tumors including HCC., In a preliminary prospective study including 31 intermediate and advanced HCC patients receiving apatinib 500 mg daily, the response rate and disease control rate (DCR) were reported as 32.26% and 80.65%, respectively. The median time to tumor progression (TTP) was 4.8 months. Furthermore, 6- and 12-month OS rates were 73.8% and 55.4%, respectively. In another recently reported retrospective study, 25 patients with unresectable or relapsed HCC were treated with apatinib until progressive disease or unacceptable toxicity. The median progression-free survival (PFS) and OS were 5 months and 13 months, respectively. The most common adverse effects were hand-foot syndrome, secondary hypertension, proteinuria, and liver dysfunction.
Recently, there have been reports indicating that apatinib combined with other therapies can be used in HCC. In a single-center, randomized controlled trial, a total of 44 patients with moderate or advanced HCC were randomly assigned with transcatheter arterial chemoembolization (TACE) alone or combined treatment of TACE with apatinib. The objective response rate (ORR) at 12 months (35% vs. 9.09%) and median PFS (12.5 vs. 6.0 months) after treatment were significantly better in the combination therapy group. Although incidences of complications related to oral apatinib such as hypertension, hand-foot syndrome, and proteinuria were higher in the combination therapy group, no severe complications were observed. Chen et al. reported similar results in a recently published retrospective study. Higher overall response rate was observed in TACE-apatinib combined group. The median TTP and OS in the TACE-apatinib group were longer than those in TACE-alone group (TTP: 6.3 vs. 3.5 months and OS: 13.0 vs. 9.9 months, respectively). Yang et al. also showed that TACE together with apatinib significantly prolonged PFS and OS in advanced HCC compared with the TACE-alone group. More recently, Xu et al. reported preliminary results of apatinib combined with SHR-1210 (anti-PD-1 antibody) for the treatment of HCC. Eight of 16 evaluable HCC patients achieved PR, including one in the apatinib 125-mg cohort and seven receiving apatinib 250 mg. The ORR and DCR were 50.0% and 93.8%, respectively. During the median follow-up duration of 7.8 months, the median PFS reached to 5.8 months. The 6-month PFS rate in patients receiving apatinib 250 mg was 51.3%, and the 9-month PFS rate was 41.0%.
The main limitation of apatinib in HCC is that most studies were single-center, small-sample retrospective studies. Hence, international, large-scale, prospective, randomized clinical trials in multicenters are expected to be conducted to demonstrate the efficacy and safety of apatinib for the treatment of HCCs. We expect promising effects of apatinib in advanced HCC in the near future.
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