Abstract P6-15-05: Randomized controlled trial of neoadjuvant eribulin mesylate versus paclitaxel in women with operable breast cancer (JONIE-3 study)

Abstract

Abstract Background: Although treatment of eribulin mesylate (E) improved overall survival in metastatic breast cancer (BC) patients, little is known about the efficacy in early BC. The hypothesis of this study is that sequential administration of E followed by FEC would have less toxic, particularly peripheral neuropathy, and also have similar effect compared to paclitaxel (P) followed by FEC as primary systemic therapy (PST) for woman with operable BC. Methods: This is a phase II multicenter open label study (UMIN000012817). Patients (pts) were randomly assigned to either E (1.4mg/m2, d1 and d8, q21 days, 4 cycles) + FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2) or P (80mg/m2, weekly, 12 cycles) + FEC as PST. HER2+ patients were allowed to receive trastuzumab. Stratification factors were ER, HER2, and menopausal status. Primary endpoint was the incidence of peripheral sensory and motor neuropathy (PSN and PMN) with Grade 1 or higher according to CTCAE ver.4.0. Secondary endpoints were pathological complete response (pCR) rates (ypT0/is/ypN0), clinical response rates (CR+PR), and adverse events. Safety was assessed in all pts who received at least one dose of the study drug. Results: Between 12/2013 to 3/2016, 121 pts were randomly assigned equally to E + FEC and P + FEC. Excluding 5 pts from the primary assessment, 116 pts (58 in each group) were included in the full analysis set. The characteristics of the pts were similar in the two arms. At the end of E or P administration, the incidences of PSN were 55.4% and 92.9% in E and P arm, respectively (p<0.001). The incidences of PMN were 25.9% and 44.9% in E and P arm, respectively (p=0.049). At the end of E or P + FEC, PSN accounts for 38.9% in E arm and 85.2% in P arm (p<0.001), and PMN accounts for 20.7% in E arm and 32.8% in P arm (p=0.201). The pCR rates in E and P arm were 20.7% and 29.8% (p=0.092). The clinical response rates in E and P arm were 82.2% and 91.0% (p=0.108). No statistical significant difference was found in efficacy of PST between E and P. Conclusion: This randomized phase II study revealed that eribulin had favorable peripheral neuropathy profile with modest efficacy in the neoadjuvant setting, compared with paclitaxel. Citation Format: Miura D, Hasegawa Y, Ishikawa T, Tachibana A, Horiguchi J, Hayashi M, Miyashita M, Kubota T, Narui K, Suzuki M, Akazawa K, Kohno N. Randomized controlled trial of neoadjuvant eribulin mesylate versus paclitaxel in women with operable breast cancer (JONIE-3 study) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-05.