The Efficacy and Safety of Apatinib for Refractory Malignancies: A Review and Meta-analysis

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the ONA take:

Apatinib (also known as YN968D1) is a novel small-molecule tyrosine kinase inhibitor (TKI) that targets VEGFR-2. Although apatinib has demonstrated broad-spectrum anticancer effect, data are challenged because the studies were single-arm, small, with differences in doses and incidences of adverse events (AEs). Therefore, these researchers conducted a meta-analysis of 21 studies that included more than 700 patients to measure the efficacy and safety of apatninib.

Cancers included in the 21 trials were: lung, liver, gastric, colorectal, and breast cancers. Efficacy was evaluated with objective response rate (ORR) and disease control rate (DCR); safety was determined using total incidence of AEs and incidence of the 3 most common grade 3-4 AEs (hypertension, hand-foot syndrome, and proteinuria).

Results of the meta-analysis suggest that treatment with apatinib resulted in good disease control, with ORR and DCR significantly increased in patients who received higher doses.

OncoTargets and Therapy
OncoTargets and Therapy

Background and purpose: Apatinib is a novel, oral, small-molecule tyrosine kinase inhibitor that targets VEGFR-2. Recent clinical trials have revealed its broad-spectrum anticancer effect. However, most recent studies of apatinib have involved single-arm studies with insufficient cases, different doses of drugs, and different incidences of adverse events (AEs), which has resulted in a lack of accurate measurement of the efficacy and safety of apatinib. Thus, we performed this meta-analysis to evaluate the efficacy and safety of apatinib.
Methods: In total, 21 studies from five databases (PubMed, ScienceDirect, ClinicalTrials.gov, China National Knowledge Infrastructure [CNKI], and Cochrane Library) were included in this meta-analysis. All statistical analyses in this meta-analysis were performed using Stata 14.0 software. We used objective response rate (ORR) and disease control rate (DCR) to evaluate the efficacy of apatinib for five major types of solid tumors. Additionally, we used the total incidence of AEs and the incidence of the three most common grade 3–4 AEs to evaluate the safety of apatinib.
Results: The pooled results for the efficacy of apatinib in the treatment of different types of solid tumors revealed that patients treated with apatinib exhibited good disease control. In addition, it was likely that an increased dose of apatinib resulted in an increased ORR in lung and breast cancer and an increased DCR in liver and gastric cancer. Although AEs appeared in 84% of patients included in this meta-analysis, most of these AEs were of grades 1–2 and were well tolerated and controlled. The most common grade 3–4 AEs included hypertension, hand-foot syndrome, and proteinuria. Importantly, there were no significant differences in these grade 3–4 AEs with higher doses of apatinib.
Conclusion: Apatinib is a novel VEGFR-2 inhibitor with proven efficacy and safety for solid tumors. The meta-analysis reveals the broad-spectrum anticancer effect of apatinib.


Keywords: apatinib, solid tumors, objective response rate, disease control rate, adverse events 

BACKGROUND AND PURPOSE

The incidence of malignant tumors has increased rapidly in recent years, especially in China. According to a report on cancer incidence and mortality in different areas of China, 3.8 million new malignant tumor cases were diagnosed in 2014. The crude incidence of malignant tumors in 2014 was 278.1/105, whereas the crude mortality was 167.89/105.1 Therefore, more effective cancer treatments are needed.

VEGF was first identified by Folkman et al in the 1970s.2 Briefly, VEGF, which is mitogenic for endothelial cells and is responsible for the formation of new capillaries, plays an important role in tumor growth and metastasis.2,3 The physiological VEGF family consists of six growth factors, namely VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and PLGF. The VEGFR family includes three protein tyrosine kinases: VEGFR-1 (Flt-1), VEGFR-2 (Flt-1/KDR), and VEGFR-3 (Flt-4). The combination of VEGF and VEGFR induces angiogenesis and vasculogenesis through p38MAPK, Raf/MEK/ERK, and PI3K/PKB signaling pathways.4,5 Given that VEGFR-2 plays a more important role in the signaling pathways, small-molecule tyrosine kinase inhibitors mostly target VEGFR-2.

Apatinib, also known as YN968D1, is a novel, oral, small-molecule tyrosine kinase inhibitor that targets VEGFR-2 as well as c-Kit and c-SRC tyrosine kinases.6 Apatinib was approved and launched in China in 2014 for subsequent-line treatment of gastric cancer.7 Recent clinical trials have revealed its broad-spectrum anticancer effect. However, most recent studies of apatinib have involved single-arm studies with insufficient cases, different doses of drugs, and different incidences of adverse events (AEs), resulting in a lack of accurate measurement of the efficacy and safety of apatinib. Thus, we performed this meta-analysis to evaluate the efficacy and safety of the novel VEGFR-2 inhibitor apatinib. 

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