Abstract: This review included 28 studies. The updated analysis included 6871 randomised women, while the original review had 3643 women. Of the 28 included studies, we considered 19 studies to be at low risk of bias overall; however, some studies failed to report details on allocation concealment and methods of outcome assessment for those outcomes that are more likely to be influenced by a lack of blinding (for example tumour response rate). Studies varied in the taxane-containing chemotherapy backbone, and the comparator arms and were categorised into three groups: Regimen A plus taxane versus Regimen A (2 studies); Regimen A plus taxane versus Regimen B (14 studies); and single-agent taxane versus Regimen C (13 studies). Thirteen studies used paclitaxel, 14 studies used docetaxel, and 1 study allowed the investigator to decide on the type of taxane; the majority of studies delivered a taxane every 3 weeks. Twenty studies administered taxanes as first-line treatment, and 21 studies involved anthracycline naïve women in the metastatic setting. The combined HR for overall survival and time to progression favoured the taxane-containing regimens (HR 0.93, 95% confidence interval (CI) 0.88 to 0.99, P = 0.002, deaths = 4477; and HR 0.92, 95% CI 0.87 to 0.97, P = 0.002, estimated 5122 events, respectively) with moderate to substantial heterogeneity across trials. If the analyses were restricted to studies of first-line chemotherapy, this effect persisted for overall survival (HR 0.93, 95% CI 0.87 to 0.99, P = 0.03) but not for time to progression (HR 0.96, 95% CI 0.90 to 1.02, P = 0.22). Tumour response rates appeared to be better with taxane-containing chemotherapy in assessable women (RR 1.20, 95% CI 1.14 to 1.27, P < 0.00001) with substantial heterogeneity across studies. Taxanes were associated with an increased risk of neurotoxicity (RR 4.84, 95% CI 3.18 to 7.35, P < 0.00001, 24 studies) and hair loss (RR 2.37, 95% CI 1.45 to 3.87, P = 0.0006, 11 studies) but less nausea/vomiting compared to non-taxane-containing regimens (RR 0.62, 95% CI 0.46 to 0.83, P = 0.001, 26 studies). Leukopaenia and treatment-related death did not differ between the two groups (RR 1.07, 95% CI 0.97 to 1.17, P = 0.16, 28 studies; and RR 1.00, 95% CI 0.63 to 1.57, P = 0.99, 23 studies, respectively). For quality of life measures, none of the individual studies reported a difference in overall or any of quality of life subscales between taxane-containing and non-taxane chemotherapy regimens. Taxane-containing regimens appear to improve overall survival, time to progression, and tumour response rate in women with metastatic breast cancer. Taxanes are also associated with an increased risk of neurotoxicity but less nausea and vomiting compared to non-taxane-containing regimens. The considerable heterogeneity encountered across studies probably reflects the varying efficacy of the comparator regimens used in these studies and indicates that taxane-containing regimens are more effective than some, but not all, non-taxane-containing regimens.

Plain-language summary: The evidence is current to February 2013. We included 28 studies that randomised 6871 women. Women were assigned to receive either a taxane-containing chemotherapy regimen (single taxane or in combination with other chemotherapy drugs) or a non-taxane chemotherapy regimen. There were variations in the taxane-containing chemotherapy regimen and the non-taxane treatments. Approximately half of the studies used paclitaxel and the other half used docetaxel, and in the majority of cases, taxanes were administered every three weeks. Of the 28 studies, 20 studies included women who received taxanes as their first treatment after their diagnosis of metastatic breast cancer, and 21 studies involved women who had not been previously treated with anthracyclines in the metastatic setting. From those studies reporting median follow-up, this ranged from 9 months to 69 months. This review showed that chemotherapy regimens including taxanes improved survival and decreased the progression of metastatic breast cancer. If the analyses were restricted to those studies where women received taxanes as their first treatment after their diagnosis of metastatic breast cancer, the survival benefit persisted. Taxanes also appeared to cause tumours to shrink more than chemotherapy regimens without taxanes. However, there were differences in side effects. The risk of experiencing neurotoxicity (tingling of hands and feet) with taxanes increased compared to non-taxane chemotherapy. Hair loss also seemed to be more likely with taxane than with non-taxane-containing regimens. However, less nausea/vomiting was observed with taxanes. There was no difference in the rates of leukopaenia (low white blood cells) or treatment-related deaths between taxane and non-taxane chemotherapy. Of the studies that reported quality of life measures, there did not appear to be any differences (overall or on subscales) in quality of life between the two groups. We considered 19 out of the 28 studies to be at low risk of bias overall. However, some studies failed to report details on concealing drug treatments and methods of outcome assessment for those outcomes more likely to be at risk of bias (for example tumour response rate). The degree of variability seen across the included studies probably reflects the varying efficacy of the non-taxane chemotherapy regimens used in these studies and indicates that taxane-containing chemotherapies are more effective than some, but not all, non-taxane-containing regimens.