Controlled trials of chemotherapy for locally advanced or metastatic breast cancer in women, aged at least 18 years, previously treated with an anthracycline and a taxane were eligible for inclusion. Trials of the following chemotherapy agents were eligible: capecitabine, gemcitabine, vinorelbine, docetaxel, paclitaxel, and paclitaxel protein-bound particles; these could be administered as monotherapy or in combination (with each other or other chemotherapy agents). Control groups could receive any drug or placebo. The authors excluded trials restricted to human epidermal growth factor receptor 2 (HER2) positive patients, trials of high-dose chemotherapy, trials where under half the participants received both an anthracycline and a taxane, and phase 1 trials.
The primary outcomes were overall survival and progression-free survival. Secondary outcomes included duration of response, overall response, toxicity, and quality of life.
Participants in the included studies were women with a median age of 51 to 58 years. The number of previous chemotherapy regimens they had received for metastatic breast cancer ranged from nil to five; most women had received one or two such regimens (where reported). The number of women with three or more metastatic sites ranged across study groups from 26 to 58% (where reported). Interventions included vinorelbine, either alone or in combination with gemcitabine or 5-fluorouracil, and capecitabine, as monotherapy or in combination with bevacizumab. It appeared that one trial compared vinorelbine or mitomycin plus vinblastine versus doxorubicin. Comparators differed across studies, and included capecitabine or vinorelbine alone, oxaliplatin and 5-fluorouracil, and pegylated liposomal doxorubicin.
A single reviewer selected studies for inclusion, checking with a second reviewer when in doubt. A second reviewer also checked 10% of the citations. Disagreements were resolved by consensus.