Research in context
Evidence before this study
At the time that this study design was finalised in 2010, we searched PubMed, with the search terms “advanced breast cancer”, “phase 3 clinical trial”, “taxane”, “anthracycline”,“capecitabine”, and major oncology society meeting websites, which showed no standard of care or universal chemotherapeutic approach for treatment of patients with advanced breast cancer who progress after an anthracycline, taxane, and capecitabine. Choice of chemotherapeutic drug was driven by the nature and timing of previous therapy, extent of disease burden, cancer-related symptoms, patient and clinician preference, and availability of specific drugs in a given country or region. Available drugs produced suboptimum outcomes and an expected survival of less than 1 year. An urgent need existed for new chemotherapeutic drugs, especially those with a non-overlapping mechanism of action to ensure no cross-resistance and reduce overlapping toxicities.
Added value of this study
It had been postulated that a drug with a different mechanism of action and non-overlapping toxicities might improve survival in patients with heavily advanced disease, especially when most of the commonly used drugs are microtubule-targeting agents. Although we did not demonstrate a significant difference between groups in overall survival, the overlapping adverse event profile and improved global quality of life are encouraging.
Implications of all the available evidence
Although there was no difference in overall survival between groups in the overall population, the suggestion of benefit with etirinotecan pegol in the predefined subgroups of patients with advanced breast cancer and a history of brain metastases and liver metastases deserves further investigation in clinical trials, as does the investigation of predictive biomarkers such as circulating tumour cells that have the potential to identify appropriate patients for treatment with this novel drug.