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Feasibility study of EndoTAG-1, a tumor endothelial targeting agent, in combination with paclitaxel followed by FEC as induction therapy in HER2-negative breast cancer

par Ignatiadis, Michail ;Zardavas, Dimitros ;Lemort, Marc ;Wilke, Celine;Vanderbeeken, M.C.;D'Hondt, Veronique ;de Azambuja, Evandro ;Gombos, Andrea ;Lebrun, Fabienne;Dal Lago, Lissandra ;Bustin, Fanny;Maetens, Marion M. ;Ameye, Lieveke;Veys, Isabelle ;Michiels, Stefan ;Paesmans, Marianne ;Larsimont, Denis ;Sotiriou, Christos ;Nogaret, Jean-Marie ;Piccart-Gebhart, Martine ;Awada, Ahmad
Référence PloS one, 11, 7, e0154009
Publication Publié, 2016-07

Article révisé par les pairs

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Résumé :

Background: EndoTAG-1, a tumor endothelial targeting agent has shown activity in metastatic triple-negative breast cancer (BC) in combination with paclitaxel. Methods: HER2-negative BC patients candidates for neoadjuvant chemotherapy were scheduled to receive 12 cycles of weekly EndoTAG-1 22mg/m2 plus paclitaxel 70mg/m2 followed by 3 cycles of FEC (Fluorouracil 500mg/m2, Epirubicin 100mg/m2, Cyclophosphamide 500mg/m2) every 3 weeks followed by surgery. Primary endpoint was percent (%) reduction in Magnetic Resonance Imaging (MRI) estimated Gadolinium (Gd) enhancing tumor volume at the end of EndoTAG-1 plus paclitaxel administration as compared to baseline. Safety, pathological complete response (pCR) defined as no residual tumor in breast and axillary nodes at surgery and correlation between % reduction in MRI estimated tumor volume and pCR were also evaluated. Results: Fifteen out of 20 scheduled patients were included: Six patients with estrogen receptor (ER)-negative/HER2-negative and 9 with ER-positive/HER2-negative BC. Nine patients completed treatment as per protocol. Despite premedication and slow infusion rates, grade 3 hypersensitivity reactions to EndoTAG-1 were observed during the 1st, 2nd, 3rd and 6th weekly infusion in 4 patients, respectively, and required permanent discontinuation of the EndoTAG-1. Moreover, two additional patients stopped EndoTAG-1 plus paclitaxel after 8 and 9 weeks due to clinical disease progression. Two patients had grade 3 increases in transaminases and 1 patient grade 4 neutropenia. pCR was achieved in 5 of the 6 ER-/HER2- and in none of the 9 ER+/HER2- BC patients. The mean % reduction in MRI estimated tumor volume at the end of EndoTAG-1 plus paclitaxel treatment was 81% (95% CI, 66% to 96%, p<0.001) for the 15 patients that underwent surgery; 96% for patients with pCR and 73% for patients with no pCR (p = 0.04). Conclusions: The EndoTAG-1 and paclitaxel combination showed promising preliminary activity as preoperative treatment, especially in ER-/HER2- patients. Further studies are warranted with need of premedication optimization. Trial Registration ClinicalTrials.gov NCT01537536.