| Added by | mollevi |
|---|---|
| Last modified by | pcoopman |
| Group name | EquipePC |
| Item Type | Journal Article |
| Title | 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 |
| Creator | Ignatiadis et al. |
| Author | M. Ignatiadis |
| Author | D. Zardavas |
| Author | M. Lemort |
| Author | C. Wilke |
| Author | M. C. Vanderbeeken |
| Author | V. D'Hondt |
| Author | E. De Azambuja |
| Author | A. Gombos |
| Author | F. Lebrun |
| Author | L. Dal Lago |
| Author | F. Bustin |
| Author | M. Maetens |
| Author | L. Ameye |
| Author | I. Veys |
| Author | S. Michiels |
| Author | M. Paesmans |
| Author | D. Larsimont |
| Author | C. Sotiriou |
| Author | J. M. Nogaret |
| Author | M. Piccart |
| Author | A. Awada |
| Abstract | 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. |
| Publication | PLoS One |
| Volume | 11 |
| Pages | e0154009 |
| Date | 2016 |
| Journal Abbr | PloS one |
| DOI | 10.1371/journal.pone.0154009 |
| ISSN | 1932-6203 (Electronic) 1932-6203 (Linking) |
| Tags | clinic |
| Date Added | 2018/11/14 - 12:07:50 |
| Date Modified | 2019/05/16 - 15:51:18 |
| Notes and Attachments | (Note) (Note) 27454930 (Attachment) |
Institut de Recherche en Cancérologie de
