Combination versus sequential single-agent therapy in metastatic breast cancer

The optimal treatment approach in metastatic breast cancer is controversial. Until recently, the arguments for administering antitumor agents sequentially in the metastatic setting have traditionally outweighed those for administering agents in combination. Older, often empirically designed drug combinations were no more effective and often more toxic than monotherapy, compromising quality of life for little or no clinical benefit. However, more recent studies show that combination and sequential therapy both have their place in the treatment of metastatic breast cancer, with the heterogeneity of breast cancer demanding flexibility in approach. Newer drug combinations, such as paclitaxel/trastuzumab or capecitabine/docetaxel, show survival advantages over single-agent therapy and have manageable safety profiles. Such combination treatments may be preferable to sequential therapy for patients requiring urgent reduction in their tumor burden. Sequential therapy allows the optimal delivery of single-drug therapy and potentially reduces the risk of toxicity, which may improve quality of life. Sequential therapy may be especially appropriate in frail or elderly patients, who may be unable to tolerate the toxicity of combination therapy, or in patients with slowly growing tumors. This article expands on these issues by reviewing trials comparing combination regimens with sequential approaches.