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BackgroundEndoTAG-1, a tumor endothelial targeting agent has shown activity in metastatic triple-negative breast cancer (BC) in combination with paclitaxel.MethodsHER2-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.ResultsFifteen 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).ConclusionsThe 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 RegistrationClinicalTrials.gov NCT01537536

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e12008 Background: Cationic liposome-encapsulated paclitaxel , a tumor endothelial targeting agent (composition of paclitaxel combined with neutral and cationic lipids) has shown activity in metastatic triple-negative breast cancer (BC) in combination with paclitaxel (Awada et al. ESMO2010). No data exist in the non-metastatic setting. Methods: HER2-negative BC candidates for neoadjuvant chemotherapy were scheduled to receive 12 cycles of weeklycationic liposome-encapsulated paclitaxel 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 tumor volume at the end of cationic liposome-encapsulated paclitaxel 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: Six patients with estrogen receptor (ER)-negative/HER2-negative and 9 with ER-positive/HER2-negative BC were included. Nine patients completed treatment as per protocol. Despite premedication and slow infusion rates, grade 3 hypersensitivity reactions to cationic liposome-encapsulated paclitaxel were observed during the 1st, 2nd, 3rd and 6th weekly infusion in 4 patients, respectively and required permanent discontinuation of the cationic liposome-encapsulated paclitaxel . Two patients stopped cationic liposome-encapsulated paclitaxel plus paclitaxel after 8 and 9 weeks due to clinical disease progression, two patients had grade 3 increase in transaminases and 1 patient grade 4 neutropenia. PCR was observed in 5 of the 6 ER-/HER2- and in none of the 8 ER+/HER2- BC patients. The median % reduction in MRI estimated tumor volume at the end of cationic liposome-encapsulated paclitaxel plus paclitaxel treatment was 90% (95% Confidence Interval: 69-99%), (p<0.001, sign test) for the 14 patients that underwent surgery; 99% (CI:87-100%) for patients with pCR and 84% (CI:50-95%) for patients with no pCR. Conclusions: The cationic liposome-encapsulated paclitaxel and paclitaxel combination showed promising preliminary activity as preoperative treatment, especially in ER-/HER2- patients. Further studies are warranted with need of premedication optimization. Clinical trial information: NCT01537536.