Interpreting metastatic breast cancer data in the latter half of this decade

The management of metastatic breast cancer has evolved considerably in the last 5-6 years and a variety of treatments have been shown to impact on the natural history of this disease over this period, with demonstration of survival prolongation justifiably generating considerable excitement. However, the question may be asked whether the success and clinical utility of novel therapies should be defined solely by this criterion. This paper will advance the view that several additional considerations should be weighed in the interpretation of data from randomised, controlled trials in determining a drug's clinical utility. The presence or absence of a survival advantage must be scrutinised in the context of the biological principles underpinning a drug's activity, the mix of patient and tumour characteristics in the population under study, the implications of 'cross-over', and the effect of other active therapies used upstream and downstream of the intervention under study, including the changing standards of adjuvant therapy. Lastly, the relative toxicity of regimens under comparison is particularly relevant to the feasibility of their wider application. In this report, each of these considerations is reviewed and their influence for trial design discussed. (c) 2006 Elsevier Ltd. All rights reserved.