Evolving Approaches to Metastatic Breast Cancer Patients Pre-treated with Anthracycline and Taxane

Abstract

Metastatic breast cancer is currently incurable and the goals of therapy focus on prolonging survival and maintaining quality of life by controlling symptoms and minimizing toxicity. Treatments for metastatic breast cancer include chemotherapeutic agents from various classes, such as taxanes, vinca alkaloids, anthracyclines and antimetabolites. This review provides an overview of chemotherapeutic agents for the treatment of metastatic breast cancer patients previously treated with anthracyclines and taxanes, focusing on a clinical evaluation of eribulin, the most recently approved agent for the treatment of metastatic breast cancer. Eribulin is a synthetic derivative of halichondrin B, a tumour growth inhibitor found in marine sponges, which prevents microtubule growth and sequesters the tubulin molecules into unusual aggregates, initiating apoptosis. Studies of eribulin have shown that the drug is effective in the treatment of previously treated metastatic breast cancer, and has an acceptable toxicity profile. Importantly, in the phase III EMBRACE study, eribulin treatment resulted in a survival advantage, a difficult endpoint to achieve with a single chemotherapeutic agent. An additional phase III study showed that eribulin has similar efficacy to capecitabine in women treated with no more than three prior therapies. Furthermore, pre-specified exploratory analyses suggest that particular patient subgroups may have greater therapeutic benefit with eribulin and may warrant further study to explore the potential mechanisms.

Combination chemotherapy with mitomycin C and methotrexate is active against metastatic HER2-negative breast cancer even after treatment with anthracycline, taxane, capecitabine, and vinorelbine

“…In vinorelbine and eribulin treatment, inhibition of mitotic spindle assembly leads to cell cycle arrest at the G2/M phase. For eribulin, although the target points are different respectively, the target molecule itself is the same as in taxane and vinorelbine (Saji 2013 ; Andreopoulou and Sparano 2013 ).…”

Eribulin mesilate versus vinorelbine in women with locally recurrent or metastatic breast cancer: A randomised clinical trial

“…Guidelines generally recommend sequential cytotoxic monotherapy for MBC, but no specific sequence of cytotoxic therapies has been advocated [1,2]; therefore, the choice is often determined by perceived relative efficacy and tolerability, the patient's comorbidities, performance status, preferences and prior adjuvant therapy. The increased use of anthracyclines and taxanes in the neo-adjuvant setting makes treatment selection at recurrence more challenging, and cumulative toxicity can limit therapeutic choices in heavily pretreated patients [4,5]. There remains, therefore, an unmet need for effective, welltolerated treatments for patients with pretreated MBC.…”

Frontiers in intravital multiphoton microscopy of cancer

“…35 At the time, eribulin appeared to be a promising chemotherapeutic agent for advanced, taxane-resistant breast cancers, 137 but only particular patient subgroups were benefiting from this drug, raising the question of its mechanism of action. 138 IV-MPM showed that eribulin is progressively delivered from the blood vessels into the tumor tissue over 2 hours and that eribulin uptake is blocked in cells with high expression of the multidrug resistance protein 1 (MDR1) known to confer resistance to taxanes by increasing drug efflux ( Figure 4A). On the basis of these results, the authors redesigned the therapeutic strategy such that an MDR1 inhibitor, HM30181, which sensitizes the MDR1-high resistant cells to eribulin, was coadministered with eribulin.…”

“…Laughney et al generated a fluorescently tagged analog of the microtubule inhibitor eribulin . At the time, eribulin appeared to be a promising chemotherapeutic agent for advanced, taxane‐resistant breast cancers, but only particular patient subgroups were benefiting from this drug, raising the question of its mechanism of action . IV‐MPM showed that eribulin is progressively delivered from the blood vessels into the tumor tissue over 2 hours and that eribulin uptake is blocked in cells with high expression of the multidrug resistance protein 1 (MDR1) known to confer resistance to taxanes by increasing drug efflux (Figure A).…”