Neoadjuvant eribulin mesylate following anthracycline and taxane in triple negative breast cancer: Results from the HOPE study.

Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy. Patients with primary triple negative breast cancer ≥2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study. In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2-5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR. Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial-mesenchymal transition, claims for further investigation. EU Clinical Trial Register, EudraCT number 2012-004956-12.

MEC, DG, LM, VT, FC, BP, GS, MCDS, MDN, AG, MPC, SF had no disclosures. SDC received speaking fees from Novartis Pharma; GVB received advisory boards from Eli Lilly, outside this work; NLV received speaking fees from Eisai, Teva and Novartis, advisory board from Celldex, research funding from Eisai, travel expenses for conferences participation from Pfizer, Gentili and Roche; AM received travel expenses for conferences participation from Brystol-Myers Squibb, Gentili, Roche and Merck; CT is a member of PLOS ONE Editorial Board. FdB received speakers bureau from BMS, ELI Lilly, Roche, Amgen, AstraZeneca, Gentili, Fondazione Menarini, Novartis, MSD, Ignyta, Bayer, Noema S.r.l., ACCMED, Dephaforum S.r.l., Nadirex, Roche, Biotechspert Lts, PriME Oncology, Pfizer, and is a consultant/advisory board member for BMS, TizianaLife Sciences, Celgene, Novartis, Servier, Phanm Research Associated, Daiichi Sankyo, Ignyta, Amgen, Pfizer, Roche, Teogarms, and Pierre Fabre. This does not alter our adherence to PLOS ONE policies on sharing data and materials.