title: A meta-analysis of combination therapy versus single-agent therapy in anthracycline- and taxane-pretreated metastatic breast cancer: results from nine randomized Phase III trials.
abstract: Nowadays, the philosophy of treating metastatic breast cancer (MBC) is slowly evolving. Especially for the anthracycline- and taxane-pretreated MBC patients, no standard therapy exists in this setting. Whether to choose doublet agents or single agent as salvage treatment remains fiercely debated. Thus, we conducted a meta-analysis to resolve this problem. Databases including PubMed, EMBASE, and Cochrane library were searched for Phase III randomized clinical trials (published before August 2015) comparing the efficacy and adverse effects between the combination therapy and single-agent therapy in anthracycline- and taxane-pretreated MBC patients. The primary end point was the overall survival (OS), and the secondary end points were the progression-free survival (PFS), overall response rate (ORR), and grade 3 or 4 toxicities. The pooled hazard ratio (HR) and pooled risk ratio (RR) were used to evaluate the efficacy. Analyses were also performed to estimate the side effects and safety of both groups. In all, nine eligible randomized clinical trials were included in this meta-analysis. Improvements were proven in the doublet agents group on OS (HR 0.90, 95% confidence interval [CI] 0.84-0.96, P=0.002), PFS (HR 0.81, 95% CI 0.76-0.88, P<0.001), and ORR (RR 1.72, 95% CI 1.34-2.21, P<0.001). Notably, subgroup analysis failed to favor the targeted agent-based combination in terms of OS (HR 1.08, 95% CI 0.89-1.31, P=0.365), PFS (HR 1.09, 95% CI 0.88-1.35, P=0.433), and ORR (RR 1.60, 95% CI 0.69-3.71, P=0.278) compared with single agent. In addition, although more hematological and gastrointestinal toxicities were observed in the doublet agents group, they were acceptable and manageable. Taken together, when compared with single-agent therapy, doublet agents should be considered a treatment option because of the superior efficacy and the manageable safety profile for the prior anthracycline- and taxane-treated MBC patients.
authors.affiliation: Department of Oncology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou; Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai.
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Prevention and Cure Center of Breast Disease, Third Hospital of Nanchang, Nanchang.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Oncology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou; Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai.
authors.forename: Chun
authors.initials: C
authors.lastname: Hu
authors.affiliation: Graduate School, Xuzhou Medical College, Xuzhou.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou; Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou; Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai.
authors.forename: Shujing
authors.initials: S
authors.lastname: Liang
authors.affiliation: Department of Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Oncology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou; Department of Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai.
authors.forename: Fengchun
authors.initials: F
authors.lastname: Zhang
keywords: anthracyclines; breast cancer; chemotherapy; combination therapy; toxicity