|Topic:||Breast cancer, advanced|
|Authors:||C. Twelves1, C. Akerele2, J. Wanders3, J.A. Cortes4; 1Leeds/GB, 2Woodcliff Lake, NJ/US, 3Hatfield/GB, 4Barcelona/ES|
Background: For pts with heavily pretreated MBC, there is a need for therapies that offer survival benefit and acceptable tolerability. Eribulin (E) is a non–taxane microtubule dynamics inhibitor with a novel mode of action, and EMBRACE is the first Phase III monotherapy study to meet its primary endpoint of prolonged overall survival (OS) (E 13.12 vs TPC 10.65 months; HR 0.81 [95% CI 0.66, 0.99] p=0.041) in such pts.
Methods: In this open-label, multicenter study, pts (N=762; 508 E, 254 TPC) with locally recurrent or MBC had received 2-5 prior chemotherapy regimens (≥2 for advanced disease), including an anthracycline and a taxane unless contraindicated. Pts were randomized 2:1 to E 1.4 mg/m2 2-5 min IV bolus on Days 1 and 8 of a 21–day cycle or TPC (cytotoxic, hormonal, or biologic monotherapy, or supportive care only). Pre-specified exploratory subgroups included hormone receptor expression status (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2 [HER2], and triple [ER/PR/HER2] negative), number of organs involved, sites of disease, and prior capecitabine.
Results: The pre-defined exploratory subgroup analyses demonstrated that in all subgroups OS benefit with E compared with TPC was maintained. For pts with ER/PR positive (n=528) and ER/PR negative (n=187) disease, HR 0.83 (95% CI 0.64, 1.06) and HR 0.66 (0.45, 0.99), respectively, were seen. In HER2 positive (n=123) and HER2 negative (n=565) subgroups, the HRs were 0.76 (0.47, 1.24) and 0.81 (0.64, 1.02), respectively. In the triple receptor (ER/PR/HER2) negative subgroup (n=144), HR 0.71 (0.46, 1.10) was observed. For ≤2 and 2 organs involved, visceral and non-visceral disease, and no or prior capecitabine, the HRs were 0.80 (0.62, 1.04) and 0.81 (0.57, 1.17), 0.77 (0.62, 0.96) and 1.04 (0.56, 1.91), and 0.94 (0.62, 1.44) and 0.77 (0.61, 0.97), respectively.
Conclusions: In heavily pretreated pts with MBC, E demonstrated a statistically significant improvement in OS by a median of 2.5 months compared with TPC. Pre-specified exploratory subgroup analyses also favoured E compared with TPC, with data that were consistent with the OS results.