Author(s): Francesca Martella [*] aff1 , Carlotta Bacci aff1 , Clara Giordano aff1 , Francesco Montagnani aff1 , Elena Gelain aff2 , Loredana Rabatti aff3 , Luisa Fioretto aff1
eribulin; metastatic breast cancer; real-life setting
In breast cancer patients, long-term survival outcomes are related to disease stage at presentation. Currently, the majority of women with early-stage disease will experience long-term disease-free survival, whereas those with advanced stages have a 5-year relative survival of only 24% and almost none of metastatic patients are cured [1 ]. Advanced breast cancer patients frequently receive multiple sequential lines of treatment even though the impact of every single line on improvement of survival is difficult to quantify and debatable. In recent months, data have clearly demonstrated survival benefit in metastatic breast cancer (MBC) with HER2 amplification due to the development of new targeted agents alone or in combination with old chemotherapies [2,3 ]. Nevertheless, 80% of patients with MBC have HER2-negative disease [ 4 ]. Although many agents are available for the systemic treatment of HER2-negative breast cancer, there is a particular need to improve the efficacy of drug therapy in this setting, especially when patients have developed resistance to anthracyclines and taxanes, used in the adjuvant and/or early line metastatic setting. Vinca alkaloids, gemcitabine or capecitabine are the mainstay in metastatic patients beyond anthracyclines and taxanes, as no gold standard option exists to date [5-7 ].
Eribulin mesylate is a structurally simplified synthetic analog of halichondrin B, which is a natural product isolated from the marine sponge Halichondria okadai . It induces irreversible mitotic block at G2-M phase and apoptosis, inhibiting microtubule polymerization without affecting depolymerization [ 8 ]. This mechanism of action is different from other tubulin-targeting agents such as taxanes, vinca alkaloids, epothilones. The Phase III EMBRACE trial investigated the efficacy of eribulin compared with treatment of physician's choice in locally advanced or metastatic breast cancer patients who had received at least two prior chemotherapy regimens, including both anthracyclines and taxanes. To our knowledge, to date, the open-label Phase III EMBRACE study is the only trial in heavily treated breast cancer showing an advantage in overall survival (OS) [9 ]. The results of the study showed that eribulin was associated with a median OS of 13.2 months, median progression-free survival (PFS) of 3.7 months and a 23% of clinical benefit, including overall response rate and stabilization (stable disease [SD]) lasting for at least 24 weeks. Moreover, the study demonstrated an acceptable toxicity profile, with limited grade (G) 3 and 4 nonhematological events (10% G3 fatigue and 7% G3 peripheral neuropathy), and only 5% of febrile neutropenia [9 ]. Thus, the EC issued in 2011 a marketing authorization valid throughout the EU for eribulin in patients with MBC, beyond anthracyclines and taxanes treatment.
On this basis, since 2012, eribulin has represented a key drug for women with MBC in the oncology unit of the Azienda Sanitaria Firenze. As part of the quality assessment of the breast cancer multidisciplinary team of Azienda Sanitaria Firenze, we evaluate here our experience with eribulin to look...