ESMO 2011 Report – EMBRACE Study: Broadening the management of heavily pre-treated metastatic breast cancer

by Dr Sunil Upadhyay – Management of heavily pre-treated metastatic breast cancer patients remains a challenge. Most emphasis is on the role of molecular agents and personalised medicine hence making them attractive topics of research. Limited new cytotoxic agents are currently under investigation. One such agent is eribulin mesylate a non-taxane microtubule inhibitor with a novel mode of action. The results of the EMBRACE study were presented at ASCO 2010 and published in Lancet on 3^rd March 2011.¹ Eribulin was found to show prolonged overall survival in heavily pre-treated metastatic breast cancer patients. However, it has been suggested that patients receiving treatment of physician’s choice (TPC) may be less likely to gain benefit if they receive therapy with a class of agent they had previously been treated with (re-challenge), thereby favouring eribulin. Therefore, a reanalysis of the EMBRACE data was conducted and the results were presented at EMCC 2011 in Stockholm by Fatima Cardose, Breast Cancer Unit and the Director of the Breast Cancer Research Program of the Champalimaud Cancer Center in Lisbon, Portugal.

The presented data excluded re-challenged patients in the TPC arm, allowing assessment of eribulin vs agents given for the first time. Along with it, eribulin versus re-challenged patients only was also assessed.

 EMBRACE exploratory OS: subgroup analysis

The re-challenged group consisted of taxanes (n=38/41), anthracyclines (n=24/24), vinorelbine (n=5/65), capecitabine (n=4/45), hormone therapy (n=4/8) and others (n=23/25). No one receiving gemcitabine was re-challenged (n=46). When the re-challenged patients were excluded from the analysis, the OS was still found to be in favour of eribulin compared to TPC (HR 0.74, p=0.014) with median overall survival of 13.11 and 10.55 months respectively, an extra benefit of 2.6 months. The reanalysis of eribulin compared to the 98 re-challenged patients in the TPC group showed median OS of 13.1 vs 10.7 months respectively (HR=0.92, p=0.557) which was not significant. Thus, eribulin demonstrated OS improvement for previously treated patients with locally recurrent or metastatic breast cancer, even when re-challenged patients were removed from the TPC arm. The results for both re-challenged and non re-challenged groups were consistent with the overall study, but did not reach statistical significance for the re-challenged group. It is important to note that the most common adverse effects for patients treated with eribulin were asthenia/fatigue, neutropaenia, alopecia, nausea and peripheral neuropathy. The neutropaenia resulted in discontinuation in <1% and peripheral neuropathy in 5% of the patients receiving eribulin.

Since the publication of these data, eribulin has been licensed and made available through the cancer drug fund route in many networks in UK. However, the formulation of the marketed drug is different and the recommended dose is 1.23mg/m2, instead of 1.4 mg/m2  for eribulin mesylate used in this trial, days 1 and 8 three weekly. (Proffered papers oral 5006, EMCC 2011)

Reference:

1. Cortes J, et al. Lancet. 2011 March 3 [Epub ahead of print]