Anthracycline- and/or taxane-resistant breast cancer: results of a literature review to determine the clinical challenges and current treatment trends

Abstract

Background: As many as 30% of women diagnosed with early breast cancer (BC) will eventually progress to or relapse with locally advanced or meta-static BC. Resistance to the commonly used chemotherapies anthracyclines and taxanes, as well as the approval of new pharmacologic options for treating BC, present important clinical, cost-effectiveness, and societal challenges.

Objectives: The aims of this work were as follows: (1) to review published evidence for potential management strategies, particularly with new therapies, for women with resistant, recurrent, or metastatic BC who have been previously treated with anthracyclines and/or taxanes; and (2) to discuss the wider burden of disease on the patient and society, and potential implications for payers and health care decision makers.

Methods: The PubMed database and relevant congress abstract databases were searched to identify clinical data with relevance to the treatment of recurrent or metastatic BC resistant to anthracyclines and/or taxanes. No date limits were applied, and the search was current as of April 17, 2009. No specific inclusion or exclusion criteria were applied; preference was given to Phase II or III clinical trials published within the past 10 years, although older studies were included if they contained data that guides current clinical practice.

Results: Sixteen of the most relevant Phase II or III studies were identified for the 4 agents currently approved for use in this setting, including capecitabine alone (2 studies), capecitabine plus docetaxel (2 studies), ixabepilone alone (5 studies), ixabepilone plus capecitabine (3 studies), gemcitabine plus paclitaxel (1 study), and nanoparticle albumin-bound paclitaxel (3 studies), with overall response rates (complete plus partial responses) ranging from 11.5% to 57%. Other relevant studies are discussed for liposomal doxorubicin, docetaxel, paclitaxel, larotaxel, and vinorelbine, as well as for the addition of biologic agents such as trastuzumab, lapatinib, and bevacizumab to ongoing chemotherapeutic regimens in resistant or metastatic BC. However, only 4 studies discussed the cost of care and cost-effectiveness of current treatment options.

Conclusions: Previous research has reported the efficacy of capecitabine, gemcitabine, nanoparticle albumin-bound paclitaxel, and ixabepilone in the treatment of metastatic BC in patients who have already been treated with anthracyclines and/or taxanes. Such patients previously had few treatment options. Ongoing investigations into novel combination regimens with these agents, including combinations with targeted agents, may further build on this progress. Further research is needed to understand the economic implications of these regimens, including the broader societal effects and the value to patients.