Traditional therapies for OC, including debulking surgery and chemotherapy, cannot yield a good response rate in all relapsed OC patients. Efforts to understand OC biology have facilitated the development of new targeted antineoplastic agents. In cancer, angiogenesis contributes to tumor growth and invasion (23). Multiple growth factors play proangiogenic roles, including VEGF, epidermal growth factor (EGF), and platelet-derived growth factors (PDGF); of these, the VEGF pathway is pivotal in angiogenesis (24). Bevacizumab, a monoclonal antibody targeting VEGF-A, has been approved for the treatment of recurrent platinum-sensitive or -resistant OC (5). Several multitargeted receptor tyrosine kinase inhibitors (TKIs), such as imatinib, cediranib, sorafenib, sunitinib, and pazopanib, target VEGFR, PDGFR, and FGFR. Many of these inhibitors have been or are being evaluated in clinical trials in OC, and some agents have exhibited inhibitory effects (5).
Most of the studies demonstrating clinical activity in advanced OC are small case reports. Only two prospective studies tested the efficacy of apatinib treatment in advanced OC. One is a single arm clinical study, which assessed the efficacy and safety of apatinib as monotherapy in patients with recurrent platinum-resistant epithelial OC (19). The ORR and DCR in 28 patients receiving apatinib 500 mg daily were 41.4% and 68.9%, respectively, and the median PFS and OS were 5.1 months and 14.5 months (19). The other study assessed the activity of apatinib plus etoposide in the treatment of patients with platinum-resistant or -refractory OC, showing an ORR of 54% and DCR of 86% (18). The toxicity of apatinib in monotherapy and combined therapy were both manageable (18, 19). In our study, we found that, in the overall population, the median PFS was 7 months, and that the ORR was 31.71% and DCR was 78.05%, supporting the clinical activity of apatinib in recurrent OC. The safety of apatinib at a dose of 500 mg daily was similar to that reported in the above studies.
The National Comprehensive Cancer Network (NCCN) guidelines for OC suggest that biochemical recurrent patients may: 1) enroll in a clinical trial; 2) delay treatment until clinical relapse; 3) receive immediate platinum-based recurrence therapy; or 4) undergo best supportive care (25). Thus, several studies aimed to investigate low-toxicity agents to delay the appearance of measurable disease in these patients (26). However, no efficacy agent was confirmed until now. In our study, we demonstrated the efficacy of apatinib in biochemical recurrent OC patients with a median PFS of 6 months. This result implied that early treatment using apatinib in biochemical-only recurrent OC may extend time to clinical disease progression and delay time to intravenous chemotherapy, with low toxicity. However, a large sample study is needed to confirm the effect of apatinib in biochemical relapse.
One of the potential shortcomings of this study is that it was a relatively small-scale retrospective study; only 19 biochemical recurrent patients were evaluable. Prospective studies on a large sample cohort are needed to confirm the value of apatinib for the treatment of biochemical relapse patients. Additionally, this study failed to find a biomarker to predict the efficacy in biochemical recurrent patients. In this study, patients experienced similar grades of AEs to previous studies of apatinib treatment in OC. Hand-foot syndrome, mucositis, fatigue, anorexia, proteinuria, and hypertension were the most common adverse effects; however, all were tolerable.
Although our study was not the first to demonstrate the efficacy and safety of apatinib in advanced OC, we also investigated the activity of apatinib in only biochemical recurrent OC patients. This study indicates that apatinib might be a new option for such patients to delay time to clinical disease progression and intravenous chemotherapy. Further large-sample prospective studies are needed to prove this effect.