Eribulin Shows Improved Overall Survival in Late-Stage Aggressive Metastatic Breast Cancer

A first-in-class chemotherapy agent, eribulin (also known as E7389), has shown that it significantly improved overall survival (OS) compared with treatment of physician’s choice (TPC) in women with metastatic breast cancer who have received at least two prior treatments. The Lancet has just published the results of the Eisai Metastatic Breast Cancer Study Assessing Physician's Choice Versus E7389 (EMBRACE) phase III trial (DOI:10.1016/S0140-6736[11]60070-6).

Skeletal formula of eribulin

Eribulin provides a novel option for breast cancer patients with advanced or recurrent disease whose cancer has not responded well to anthracycline and taxane treatment. Currently there is no standard of care for these patients. Eribulin was shown to increase the median overall survival by 2.5 months compared to TPC. Women given eribulin lived for a median of 13.1 months compared with 10.6 months for women treated with physician-chosen therapies. The one-year survival rate was 53.9% for patients treated with eribulin compared to 43.7% for those treated with other therapies. The median progression-free survival was 3.7 months with eribulin and 2.2 months with TPC. 

762 heavily pre-treated (median of four previous treatments) breast cancer patients were randomized 2:1 to receive either eribulin or TPC. 96% of the TPC cohort received chemotherapy. 12% (57 patients) of patients receiving eribulin and 5% (10 patients) of TPC patients had a partial response to their treatment. Three patients had a complete response in the eribulin group (1%) and none in the TPC group. 

The benefit of eribulin treatment was achieved with manageable toxicity. 25% of eribulin-treated patients had serious adverse events, comparable to the 25% seen in the TPC group. The most notable grade 3 adverse event in the eribulin-treated cohort was neutropenia. The most common side effect of the treatment was fatigue. Peripheral neuropathy or tingling and numbness of the fingers and toes was the most common reason for discontinuation of treatment. This occurred in 24 of the 503 patients on eribulin. The study notes that patients with grade 3 and 4 peripheral neuropathy who continued treatment improved to lower grade neuropathy after dose reductions and partial delays in treatment. 

This is an important study, as pointed out by key opinion leaders, that is likely to change standard of care. It’s important to note that the authors of the trial emphasize that this is not a curative treatment. However, the study showed a benefit in overall survival, something that is quite difficult to do in such a heavily treated metastatic cancer population. As one of the authors noted, it is challenging the notion that overall survival is not an attainable endpoint in this group of women. 

The debate of whether surrogate markers for survival in metastatic cancers are appropriate is still going strong. As the paper points out, only five of 75 phase III systemic therapy trials in metastatic breast cancer used overall survival as the primary endpoint. None of the five met this endpoint. The 15 that showed overall survival did so as a secondary endpoint, and none of the studies were in metastatic breast cancer patients that were pretreated with both anthracycline and a taxane.

The EMBRACE phase III trial has likely set a new standard and exhibits an important new option in treatment. This is good news for those breast cancer patients with aggressive late-stage disease who have previously had limited options.