Overall survival in metastatic breast cancer: always our quest but not necessarily a primary endpoint

Excerpt

Valachis et al. in their article “Bevacizumab in metastatic breast cancer: a meta-analysis of randomized controlled trials” address an important development in breast cancer management. The use of bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor (VEGF), in combination with chemotherapy has been approved for first line therapy of metastatic breast cancer. This approval was the basis of an improvement of Progression Free Survival (PFS) in patients who received weekly paclitaxel plus bevacizumab compared to paclitaxel alone [1]. This was an open label protocol. Subsequently, there have been two additional first line studies, both with a placebo arm, and both showing an improvement in PFS [2, 3] In one study, in addition to taxanes, there were other common chemotherapy agents used in breast cancer (anthracycline containing combination and capecitabine) and they also showed an improvement in PFS. All three studies had Overall survival (OS) as a secondary endpoint. None of the studies demonstrated an improvement in OS. Advocates of OS argue that this metric is the “gold standard”. If there is no improvement in OS, a true therapeutic benefit has not being obtained. The intervention is marginal and it should not be adopted. This argument gains even more support if the intervention is expensive and uses significant health care resources. So should we care? …