Eribulin mesylate (ERI) is a microtubule dynamics inhibitor that has been demonstrated to prolong overall survival in metastatic breast cancer . Recently, ERI has shown to reduce the abnormality of the tumor microenvironment. Endocrine therapy has been reported to be ineffective under hypoxic conditions; however, improved oxygenation of the peritumoral area due to ERI may increase the sensitivity of endocrine therapy. Generally, the efficacy of endocrine therapy at late-line treatment is inferior to that of endocrine therapy at early-line. Hence, we hypothesized that endocrine therapy following ERI administration might be more effective.
Since the approval of ERI in Japan, 178 patients with metastatic breast cancer received ERI from August 2011 to October 2014 at the Cancer Institute Hospital. Of those, we assessed the time to treatment failure (TTF) of endocrine therapies provided to 25 postmenopausal patients in whom at least two endocrine therapies had been performed before ERI and at least one endocrine therapy after ERI. We retrospectively analyzed the effectiveness of the endocrine therapies on the basis of intraindividual changes.
In these 25 cases, TTF of endocrine therapy before ERI administration (N-1) was longer in 6 cases (24%) compared with that of N-2, which is another endocrine therapy before N-1. In contrast, TTF of endocrine therapy after ERI administration (N) was found to be longer than that of N-1 in 16 cases (64%).Thus, the ratio that the TTF of late endocrine therapy was longer than that of early endocrine therapy was significantly higher (p = 0.018) when the ERI administration was inserted between endocrine therapies.
In the present study, ERI administration between two endocrine therapies prolonged the TTF in majority of the cases, and ERI might improve the sensitivity of endocrine therapy.
Clinical trial identification
Legal entity responsible for the study
Cancer institute hospital of JFCR
Y. Ito: Research grants from Novartis, Chugai,and Parexel. N. Ishizuka: Former employee of Sanofi Honorarium from Eli Lilly. S. Takahashi: Honorarium from Eisai. S. Ohno: Honoraria from Chugai and AstraZeneca. All other authors have declared no conflicts of interest.