Evaluation of safety and efficacy of apatinib combination with chemotherapy for ovarian cancer treatment: a systematic review and meta-analysis

Background: Apatinib in combination with chemotherapy (CT) has been used in the treatment of ovarian cancer (OC), however, the safety and efficacy are unclear. The study aims at systematic evaluation of the safety and efficacy of the apatinib targeted therapy in combination with CT for the treatment of patients with advanced OC. Methods: Literature about randomized controlled clinical trials was searched using search engines such as PubMed, EMBASE, Web of Science, CNKI, the Cochrane Library, CBM, VIP and the Wanfang. We collected the related clinical studies of apatinib in combination with CT in the treatment of OC. The duration of the data retrieval related to clinical studies was from the database establishment to September 2020. Adverse reactions (ADRs) due to treatment, disease control rate (DCR), and that of objective response rate (ORR), were collected as indicators to show treatment outcomes. The literature was independently screened by two researchers. They extracted the data and evaluated the risk of biases of the included studies. Then, Revman 5.4 software was employed for performing the meta-analysis. Results: Twelve randomized controlled clinical trials with 698 patients having an advanced stage of OC were included. The results revealed that in comparison with the treatment with only CT, apatinib targeted therapy combination with CT showed significant improvement in the patients' ORR [OR = 3.19, 95% CI: (2.06, 4.94), P<0.00001] and DCR [OR = 4.97, 95% CI: (2.90, 8.52), P<0.00001]. The group that was treated with a combined therapy had shown proteinuria in higher amount (OR = 3.08, 95% CI: 51.13-8.42, P<0.00001), while the analyses of other ADRs, such nausea and vomiting (OR = 1.10, 95% CI: 0.67-1.79, P=0.71), hand-foot syndrome (OR = 1.73, 95% CI: 0.97-3.10, P=0.06), hypertension (OR = 1.18, 95% CI: 0.73-1.91, P=0.0.51), diarrhea (OR = 1.05, 95% CI: 0.56-1.97, P=0.87), leucopenia (OR = 1.22, 95% CI: 0.70-2.12, P=0.48), and myelosuppression (OR =1.00, 95% CI: 0.28-3.62, P=1.00), did not show any significant difference (P>0.05). Discussion: The effects of apatinib combination with CT for the treatment of OC are significantly better than the CT used alone in ORR and DCR, despite with a relative low incidence of adverse effects. However, due to the very low number of studies available, the results need to be further verified using a high-quality, large sample and long-term studies.