Research in context
Evidence before this study
We searched PubMed from Nov 23, 2005, to June 1, 2015, with the terms “first-line” and either “advanced breast cancer” or “metastatic breast cancer” for full text original articles. We found no phase 2 or phase 3 trials of S-1 for metastatic breast cancer. One phase 3 trial assessed oral fluorouracil derivatives. The TURANDOT trial compared the efficacy of bevacizumab plus paclitaxel versus bevacizumab plus capecitabine. In a planned interim analysis, the predefined criterion for non-inferiority of overall survival was not met.
Added value of this study
To our knowledge, this study is the first phase 3 trial of S-1 in metastatic breast cancer. This trial showed that S-1 was non-inferior to taxane with respect to overall survival and was superior to taxane with respect to health-related quality of life. In addition, adverse events such as hair loss, peripheral neuropathy, and oedema were less common in patients treated with S-1.
Implications of all the available evidence
Our findings suggest that S-1 might provide clinical benefit as first-line treatment for patients with HER2-negative metastatic breast cancer. Our study not only provides evidence to support the use of an oral fluoropyrimidine as first-line chemotherapy, but also satisfies the need for patient choice of treatment. S-1 should be considered a new standard treatment for this setting. To support this strategy, we are doing another similar trial (SELECT BC-CONFIRM, UMIN000005449) comparing overall survival of anthracycline-containing regimens versus S-1 as first-line chemotherapy for metastatic breast cancer.