Vinorelbine With Capecitabine, an Evergreen Doublet for Advanced Breast Cancer: A Systematic Literature Review and Pooled-Analysis of Phase II-III Studies

Metastatic breast cancer (MBC) is treated with cytotoxic drugs or endocrine agents according to the site and extent of the disease, biology, previous treatments, and the patient's condition, comorbidities, and wishes. In MBC, vinorelbine (VRB) and capecitabine (X; VRB + X) are chemotherapy drugs that hold activity as first or later lines of therapy. We conducted a systematic literature review and meta-analysis to quantify the efficacy of the VRB + X combination in HER2-negative (HER2^-) MBC. We searched PubMed, EMBASE, SCOPUS, Web of Science, the Cochrane Library, and CINAHL for phase II/III clinical trials that assessed VRB + X for patients with HER2^- MBC. Pooled estimates of the overall response rate (RR), median progression-free survival (PFS), and overall survival (OS) were computed using random or fixed effects models. Twenty-seven studies were included in the analysis, encompassing a total of 1356 MBC patients. All were phase II (n = 21) or prospective/pilot (n = 5) trials, except for 1 that was a phase III controlled trial. The pooled estimate for the RR in first-line therapy (n = 16 trials) was 52.9% (95% confidence interval [CI], 46.5%-59.2%). For second-line trials, data were available in n = 9 studies and the overall RR was 41% (95% CI, 31.2%-51.6%). The pooled estimates for median PFS and OS in first-line therapy were 7.3 (95% CI, 6.2-8.3) and 22.3 (95% CI, 20-24.5) months, respectively. Vinorelbine + X, with the dose and schedules currently used in clinical practice, appears to be an effective and feasible chemotherapy for MBC, for first- and also for second-line therapy.