Ovarian carcinoma has the highest mortality rate among gynecologic malignancies. Primary drug resistance and multi-drug resistance are major clinical obstacles to treatment and is the main reason for the dismal 5-year survival rate of patients. Apatinib is independently developed in China as an effective small-molecule tyrosine kinase inhibitor. It mainly functions by competitively blocking the binding of VEGF with VEGFR-2 and auto-phosphorylation of VEGFR-2, thereby inhibiting the function of VEGF in stimulating endothelial cell proliferation and migration and reducing microvascular density to elicit its anti-tumor effects.
This study is a prospective, open label, single-arm clinical trial aimed to evaluate the efficacy and safety of apatinib mesylate as treatment after failure of second-line chemotherapy in patients with advanced epithelial ovarian cancer. The study enrolled 20 patients, and 17 were evaluated. Patients received an oral dosage of apatinib (500 mg or 250 mg) once daily for 28 days as an observation cycle. The efficacy of the treatment was evaluated after three treatment cycles. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and adverse events (AEs) were assessed.
After 3 cycles of treatment, 6 (35.3%) and 2 (11.8%) patients achieved partial response (PR) and stable disease (SD), respectively. The ORR and DCR were 35.3% and 47.1%, respectively. The efficacy of apatinib was not significantly different between patients with initial dosages of 500 mg (ORR, 30%; DCR, 30%) and 250 mg (ORR, 42.8%; DCR, 71.4%). The median PFS was 2.2 months (95% confidence interval (CI), 1.0m-8.9m) and the median OS was 6.3months (95% CI, 1.5m-12.8m). The most common AEs were hypertension (70.6%), hand-foot syndrome (52.9%), and oral mucosa damage (35.3%).
In conclusion, oral apatinib treatment was efficacious, safe, and had no serious adverse effects in patients with advanced EOC who failed second-line chemotherapy.
Clinical trial identification
ChiCTR-OOC-16008034. Registration time: 2016-03-01.
Legal entity responsible for the study
Gynecologic Department of Traditional Chinese Medicine, Changhai Hospital.
CSCO-Hengrui Cancer Research Fund (No. Y-HR2015-244).
All authors have declared no conflicts of interest.