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Bevacizumab combined with chemotherapy for ovarian cancer: an updated systematic review and meta-analysis of randomized controlled trials.

ABSTRACT: This meta-analysis was updated with results from a new trial and final data to reassess the efficacy and safety of bevacizumab combined with chemotherapy in ovarian cancer (OC).Randomized controlled trials (RCTs) were searched in PubMed, EMBASE, Cochrane clinical trials, Web of Science and clinicaltrial.gov databases. Outcomes included the progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and common adverse events. The hazard ratio (HR), risk ratio (RR) and odds ratio (OR) were pooled when the meta-analysis was performed.Five RCTs with 4994 patients were included. In overall newly diagnosed OC, bevacizumab combined with chemotherapy did not significantly improve PFS (HR 0.85, 95%CI 0.70-1.02) or OS (HR 0.94, 95%CI 0.84-1.05). In the high-risk progression subgroup, the addition of bevacizumab significantly improved PFS (HR 0.76, 95%CI 0.68-0.84) and OS (HR 0.85, 95%CI 0.74-0.96). In recurrent OC, the addition of bevacizumab to chemotherapy significantly extended PFS (HR 0.53, 95%CI 0.45-0.63) and OS (HR 0.87, 95%CI 0.77-0.99). The ORR was improved (OR 2.37, 95%CI 1.99-2.82) in the overall population. Bevacizumab increased the incidence of hypertension (RR 21.27, 95%CI 9.42-48.02), proteinuria (RR 4.77, 95%CI 2.15-10.61), bleeding (RR 3.16, 95%CI 1.59-6.30), GI perforations (RR 2.76, 95%CI 1.51-5.03), arterial thrombosis events (RR 2.39, 95%CI 1.39-4.10) and venous thrombosis events (RR 1.43, 95%CI 1.04-1.96).Bevacizumab combined with chemotherapy significantly improved PFS and OS in both patients with high-risk of progression and patients with recurrent OC, with an increased incidence of common adverse events. However, no statistically significant survival benefit was identified in the front-line settings.

SUBMITTER: Wu YS

PROVIDER: S-EPMC5354693 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Bevacizumab combined with chemotherapy for ovarian cancer: an updated systematic review and meta-analysis of randomized controlled trials.

Wu Yu Shen YS Shui Lin L Shen Dan D Chen Xiaopin X

Oncotarget 20170201 6

<h4>Background</h4>This meta-analysis was updated with results from a new trial and final data to reassess the efficacy and safety of bevacizumab combined with chemotherapy in ovarian cancer (OC).<h4>Methods</h4>Randomized controlled trials (RCTs) were searched in PubMed, EMBASE, Cochrane clinical trials, Web of Science and clinicaltrial.gov databases. Outcomes included the progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and common adverse events. The hazard ...[more]

PMID: 27793044

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Project description:BackgroundRecent studies showed inconsistent results of bevacizumab combined with chemotherapy vs single-agent therapy in terms of their safety and efficacy for the treatment of recurrent glioblastoma. Therefore, we performed a meta-analysis to explore the value of bevacizumab combined with chemotherapy and single-agent therapy in recurrent glioblastoma treatment.MethodsDatabases such as MEDLINE, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) related to the topic of bevacizumab combined with chemotherapy and single-agent therapy as treatments for recurrent glioblastoma from January 1980 to April 2018. Subsequent articles were then sorted, evaluated, and analyzed.ResultsWe pooled 1,169 patient cases from seven RCTs. Bevacizumab combined with chemotherapy showed a significantly improved progression-free survival (PFS) (HR=0.65; 95% CI 0.57-0.74; P<0.001) compared to single-agent therapy. In addition, the overall survival (OS) rate showed insignificant differences between the two groups (HR=0.96; 95% CI 0.83-1.12; P=0.622). Simultaneously, we found that bevacizumab combined with chemotherapy had a higher objective response rate (ORR) (OR=2.10; 95% CI 1.32-3.33; P=0.002), but also higher incidence of adverse events (AEs) (OR=1.85; 95% CI 1.26-2.71; P=0.002). However, in subgroup analysis, we found that AEs showed insignificant differences between the two treatment methods when bevacizumab was used as the single-agent therapy subgroup (P=0.058). In addition, in the subgroup with low corticosteroid use rate at baseline (N<50%), ORR (P=0.108) and AEs (P=0.134) showed insignificant differences between the two groups.ConclusionBevacizumab combined with chemotherapy can significantly improve PFS and ORR, but did not prolong OS in these studies, and can even lead to higher odds of AEs. In addition, bevacizumab may play a dominant role and corticosteroid may be an unfavorable factor in the combination therapy of recurrent glioblastoma.

Project description:BACKGROUND:Angiogenesis inhibitors showed activity in ovarian cancer, but preliminary data could not accurately reflect the survival benefit. We thus did a systematic review and meta-analysis of randomized controlled trials to reassess the efficacy and safety of angiogenesis inhibitors combined with chemotherapy for ovarian cancer. METHODS:We searched PubMed, EMBASE, Cochrane, and ClinicalTrials.gov for randomized controlled trials comparing angiogenesis inhibitors containing therapy with conventional chemotherapy alone or no further treatment. Our main outcomes were the progression-free survival (PFS), overall survival (OS), and common adverse events. RESULTS:Fifteen trials were included (N = 8721 participants). For newly diagnosed ovarian cancer, combination treatment with angiogenesis inhibitors and chemotherapy yielded a lower risk of disease progression (hazard ratio [HR], 0.83; 95% confidence interval (CI), 0.71-0.97) and no improved OS (HR, 0.95; 95% CI, 0.86-1.05). In the high-risk progression subgroup, the addition of bevacizumab significantly improved PFS (HR, 0.72; 95% CI, 0.65-0.81) and OS (HR, 0.84; 95%CI, 0.74-0.96). In recurrent patients, the combined HR was 0.58 (95% CI, 0.52-0.65) for PFS, and for OS, the combined HR was 0.86 (95% CI, 0.79-0.94). We found no significant improvement for either PFS (HR, 0.80; 95% CI, 0.63-1.01) or OS (HR, 1.06; 95% CI, 0.88-1.28) in the pure maintenance therapy.In the overall population, angiogenesis inhibitors increased the incidence of gastrointestinal perforation (risk ratio [RR], 2.57; 95% CI, 1.66-3.97), hypertension (RR, 7.60; 95% CI, 2.79-20.70), arterial thromboembolism (RR, 2.27; 95% CI, 1.34-3.84), proteinuria (RR, 4.31; 95% CI, 2.15-8.64), and complication of wound healing (RR, 1.72, 95% CI, 1.12-2.63). CONCLUSIONS:Combination treatment with angiogenesis inhibitors and chemotherapy significantly improved PFS and OS in both patients with high-risk of progression and recurrent ovarian cancer, with an increased incidence of common adverse events. Conversely, we detected no statistically significant survival benefit in the pure maintenance setting. The main limitation of the review is clinical heterogeneity across the studies.

Project description:Antiangiogenesis therapy has been demonstrated to prolong the free survival with tolerable toxicity. However the efficacy of these drugs in overall survival (OS) remains controversial. This study was designed to assess the overall performance of antiangiogenesis therapy in improving the survival of ovary cancer (OC) patients.Electronic database of PubMed, Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched to identify relevant clinical randomized control trial (RCTs) assessing the therapeutic value of antiangiogenesis therapy in OC patients during 2011 to 2017. Additionally, abstracts of annual meetings were also conducted. Only English articles were considered. Progression free survival (PFS), OS, and objective response rate (ORR) were obtained from eligible RCTs. The HRs for time-to-event variables and ORs for dichotomous outcomes with their 95% CIs were used for this meta-analysis. All the statistical analyses were carried out by Stata 11.0 software using a fixed or random-models according to heterogeneity.A total of 15 RCTs including 9359 patients were recruited into this meta-analysis. Addition of antiangiogenic agents improved PFS (HR?=?0.71, 95% CI 0.62-0.81, P?<?.001), OS (HR?=?0.92, 95% CI 0.86-0.98, P?=?.008) and ORR (OR?=?1.74, 95% CI 1.27-2.39, P?=?.001) compared to placebo or chemotherapy alone in overall analysis. Antiangiogenic agents prolonged both PFS (HR?=?0.58, 95% CI 0.52-0.65, P?=?.000) and OS (HR=0.84, 95% CI 0.76-0.92, P?=?.000) in recurrent settings but only PFS in primary settings (HR?=?0.88, 95% CI 0.79-0.98, P?=?.020), longer PFS and OS in both platinum-sensitive recurrent patients (HR?=?0.56, 95% CI 0.48-0.64, P?=?.000, PFS; HR?=?0.86, 95% CI 0.76-0.98, P?=?.027, OS) as well as platinum-resistant recurrent cases (HR?=?0.54, 95% CI 0.41-0.71, P?=?.000, PFS; HR?=?0.84, 95% CI 0.71-0.98, P?=?.029, OS). Throughout therapy improved PFS (HR?=?0.66, 95% CI 0.57-0.76, P?<?.001) and OS (HR?=?0.89, 95% CI 0.83-0.96, P?=?.001). However the maintenance therapy of antiangiogenic agents was irrelevant to a longer PFS or OS.Based on the available studies, antiangiogenic agents play an important role in the survival of OC patients. More randomized controlled trials are needed to reach more convinced conclusion.

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Bevacizumab combined with chemotherapy for ovarian cancer: an updated systematic review and meta-analysis of randomized controlled trials.

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Bevacizumab combined with chemotherapy for ovarian cancer: an updated systematic review and meta-analysis of randomized controlled trials.

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