Chongzhen Guo1,2, Chengda Yan1,2, Lianyue Qu1,2, Rongrong Du1,2, Jianyang Lin3,4. 1. Department of Pharmacy, The First Hospital of China Medical University, Nanjing Street No. 155, Heping District, Shenyang City, 110001, Liaoning, China. 2. School of Pharmaceutical Science, China Medical University, Puhe Road No.77, Shenyang City, 110122, Liaoning, China. 3. Department of Pharmacy, The First Hospital of China Medical University, Nanjing Street No. 155, Heping District, Shenyang City, 110001, Liaoning, China. linjianyangydyy@126.com. 4. School of Pharmaceutical Science, China Medical University, Puhe Road No.77, Shenyang City, 110122, Liaoning, China. linjianyangydyy@126.com.
Abstract
PURPOSE: To evaluate the efficacy and toxicity of angiogenesis inhibitors for the treatment of ovarian cancer patients, we conducted a meta-analysis of the published literature on this subject. METHODS: In this meta-analysis, we searched PubMed, EMBASE, Web of Science, and Cochrane Library databases for randomized controlled trials (RCTs). The literature search was performed up to August 12, 2019. The risk of bias of the included studies was evaluated using The Cochrane Collaboration's tool, and the statistical analyses were performed using RevMan 5.3 software. The sensitivity analysis was performed with Stata 12.0 software. RESULTS: 22 RCTs with 11,254 patients were included. Our meta-analysis demonstrates that angiogenesis inhibitors therapy can significantly improve progression-free survival (PFS) (hazard ratio [HR] 0.71, 95% CI 0.63-0.79, I2 = 80%, P < 0.00001) and overall survival (OS) (HR 0.95, 95% CI 0.90-0.99, I2 = 0%, P = 0.03) in ovarian cancer patients. The subgroups results suggest differences in the benefit in OS in first-line treatment (HR 1.00, 95% CI 0.93-1.08, I2 = 0%, P = 0.90) compared with treatment at relapse (HR 0.87, 95% CI 0.81-0.95, I2 = 0%, P = 0.0008). The PFS improved both in first-line treatment (HR 0.87, 95% CI 0.79-0.95, I2 = 60%, P = 0.003) and recurrent treatment (HR 0.60, 95% CI 0.53-0.67, I2 = 57% P < 0.0001) patients. The PFS and OS in recurrent group were prolonged both in the platinum-resistant group(PFS: HR 0.50, 95% CI 0.42-0.60, I2 = 0%, P < 0.00001; OS: HR 0.76, 95% CI 0.62-0.93, I2 = 0%, P = 0.007) and the platinum-sensitive group (PFS: HR 0.58, 95% CI 0.49-0.69, I2 = 64%, P < 0.00001; OS: HR 0.88, 95% CI 0.79-0.99, I2 = 0%, P = 0.03). However, this therapy is associated with a higher risk of common adverse events of grade ≥ 3 (risk ratio [RR]: 1.12; 95% CI 1.07-1.17; I2 = 0%, P = 0.68) such as arterial thromboembolic disease, ascites, diarrhea, gastrointestinal perforations, headache, hemorrhagic, hypertension, hypokalemia, leucopenia, pain, proteinuria, thrombocytopenia, and thrombosis or embolism. CONCLUSION: This meta-analysis suggests angiogenesis inhibitors may significantly improve PFS and OS of ovarian cancer patients and increase the incidence of common adverse events.
PURPOSE: To evaluate the efficacy and toxicity of angiogenesis inhibitors for the treatment of ovarian cancerpatients, we conducted a meta-analysis of the published literature on this subject. METHODS: In this meta-analysis, we searched PubMed, EMBASE, Web of Science, and Cochrane Library databases for randomized controlled trials (RCTs). The literature search was performed up to August 12, 2019. The risk of bias of the included studies was evaluated using The Cochrane Collaboration's tool, and the statistical analyses were performed using RevMan 5.3 software. The sensitivity analysis was performed with Stata 12.0 software. RESULTS: 22 RCTs with 11,254 patients were included. Our meta-analysis demonstrates that angiogenesis inhibitors therapy can significantly improve progression-free survival (PFS) (hazard ratio [HR] 0.71, 95% CI 0.63-0.79, I2 = 80%, P < 0.00001) and overall survival (OS) (HR 0.95, 95% CI 0.90-0.99, I2 = 0%, P = 0.03) in ovarian cancerpatients. The subgroups results suggest differences in the benefit in OS in first-line treatment (HR 1.00, 95% CI 0.93-1.08, I2 = 0%, P = 0.90) compared with treatment at relapse (HR 0.87, 95% CI 0.81-0.95, I2 = 0%, P = 0.0008). The PFS improved both in first-line treatment (HR 0.87, 95% CI 0.79-0.95, I2 = 60%, P = 0.003) and recurrent treatment (HR 0.60, 95% CI 0.53-0.67, I2 = 57% P < 0.0001) patients. The PFS and OS in recurrent group were prolonged both in the platinum-resistant group(PFS: HR 0.50, 95% CI 0.42-0.60, I2 = 0%, P < 0.00001; OS: HR 0.76, 95% CI 0.62-0.93, I2 = 0%, P = 0.007) and the platinum-sensitive group (PFS: HR 0.58, 95% CI 0.49-0.69, I2 = 64%, P < 0.00001; OS: HR 0.88, 95% CI 0.79-0.99, I2 = 0%, P = 0.03). However, this therapy is associated with a higher risk of common adverse events of grade ≥ 3 (risk ratio [RR]: 1.12; 95% CI 1.07-1.17; I2 = 0%, P = 0.68) such as arterial thromboembolic disease, ascites, diarrhea, gastrointestinal perforations, headache, hemorrhagic, hypertension, hypokalemia, leucopenia, pain, proteinuria, thrombocytopenia, and thrombosis or embolism. CONCLUSION: This meta-analysis suggests angiogenesis inhibitors may significantly improve PFS and OS of ovarian cancerpatients and increase the incidence of common adverse events.
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