Abstract P3-14-16: A phase 2 trial of myocet®, cyclophosphamide +/- trastuzumab followed by weekly paclitaxel +/- trastuzumab as primary systemic therapy in operable and locally advanced breast cancer
Authors: Pistilli B , Rossi D , Benedetti G , Baldelli AM , Decembrini-Cognigni P , Casadei V , Ciccioli G , Ranaldi R , Fiorentini G , Latini L 
Published: August 2014

Abstract
BACKGROUND: Anthracycline- and taxane-based chemotherapies are highly effective in primary systemic treatment of breast cancer (BC). Myocet® (M) is a non-pegylated liposomal doxorubicin exhibiting reduced cardiotoxicity as compared to doxorubicin. Combination of M and cyclophosphamide (C) has demonstrated efficacy in first line treatment of metastatic BC, however few data are available in neoadjuvant setting, especially in combination with trastuzumab (T). The aims of the study were activity, in terms of pathological complete response (pCR; ie, no remaining invasive tumor in breast and lymphnodes) and safety of a sequential schedule of M and C +/- T followed by weekly paclitaxel (P) +/- T. METHODS: Estrogen receptor (ER), progesterone receptor (PgR), HER2 positivity (defined as 3+ overexpression by immunoistochemical testing or HER2 amplification by fluorescent in situ hybridisation) and Ki67 index were assessed in core needle biopsies at baseline and in residual tumour after chemotherapy. Patients with stage II/III BC received 4 cycles of MC (myocet 60 mg/m2, cyclophosphamide 600 mg/m2 on day 1 every 3 weeks), followed by 12 weekly doses of P (paclitaxel 80 mg/m2); all patients with HER2+ disease received T in combination with chemotherapy (trastuzumab loading dose of 8 mg/kg followed by 3 cycles of 6 mg/kg alongside MC; 2 mg/kg per week with the following 12 P administrations). RESULTS: 49 patients were enrolled, with 44 patients having completed chemotherapy and undergoing surgery to date. Median age was 56 years (range, 34 to 72). Tumour characteristics were as follows: stage IIA 10 patients, IIB 16, IIIA 13, IIIB 5, IIIC 1, and 4 patients with inflammatory BC; ER+/PgR+ 21 patients, ER+/PgR- 13, triple negative 8, HER2+ 16; Ki67&gt; 15% in 41 patients. Forty-four patients were evaluable for pathological response. pCR was obtained in 12 patients (27.3%). The rate of pCR in HER2+ and HER2- BC was 57.1% and 13.3%, respectively. Clinical response was obtained in 36 out of 41 clinically evaluable patients (87.8%): CR in 20 (48.8%) and PR in 16 (39%). Conservative surgery was performed in 16 patients (36.4%) and mastectomy in 28 (63.6%). The most frequently observed grade 3-4 AEs were: alopecia 47 patients (95.9%), grade 3 neutropenia 2 (4.1%), febrile neutropenia 2 (4,1%), grade 3 paresthesia 2 (4.1%), grade 3 vomiting 1 (2%), grade 3 cutaneous erythema 1 (2%). Only 1 patient experienced an asymptomatic decrease of ejection fraction lower than 50%. Five patients (10.2%) discontinued treatment with M+C because of: allergic reaction to M in 3 patients, grade 2 liver toxicity in 1 and grade 3 vomiting in 1. All of them completed the following treatment with P. Three patients (6.1%) discontinued P because of: allergic reaction in 1 patient, infectious pneumonia in 1 and grade 3 cutaneous erythema in 1. CONCLUSIONS: The use of M in this sequential anthracycline- and taxane-based regimen resulted tolerable even in combination with T and active despite of the high rate of patients with ER+ disease and with locally advanced cancer. Consistently with previous data, pCR was higher in patients with HER2+ BC.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-16.