P3-16-13: Cardiac Safety of Non-Pegylated Liposomal Doxorubicin and Docetaxel as 1st Line Treatment in Metastatic HER2 Negative Breast Cancer (Myotax Study).

Abstract

Abstract Background: Doxorubicin (DOX) is an effective, but cardiotoxic agent in metastatic breast cancer (BC). Incidence of heart failure (HF) is 2–4% and increases considerably with cumulative doses over 450–550 mg/m2. In Myocet® DOX is encapsulated in liposomes. It is delivered predominantly to areas with increased capillary permeability such as tumors and reduces cardiac exposure. We conducted an open non-comparative study to assess cardiac safety of Myocet® combined with docetaxel. Materials and methods: Females with locally advanced or metastatic HER2 negative BC. 6 cycles of Myocet® 60 mg/m2 and docetaxel 75 mg/m2 q3w as 1st line therapy. Left ventricular ejection fraction (LVEF) and disease status were assessed after cycle 2,4 and 6. Primary endpoint: signs and symptoms of HF (NYHA III-IV) or LVEF <50% and decrease ≥5% (with symptoms) or ≥10% (without symptoms). Results: 68 patients (pats) were included. Mean (sd;range) age 56,3 y (10,2;32-79), mean disease duration 5,5 y (5,1 y;1 mo-19 y), 31 pats had anthracyclines (AN) in the past. 49 pats completed all 6 cycles. Mean LVEF (%) over time are presented in table 1. 4 pats (3 AN pretreated) met the LVEF criteria for cardiotoxicity (no signs/symptoms of HF) after the 6th cycle. In 3 pats (all AN pretreated) a significant drop in LVEF was given as (one of the) reason(s) for premature discontinuation, but LVEF criteria for cardiotoxicity were not met. 73 grade ≥3 toxicities occurred in 32 pats; most frequent: neutropenia (±fever) 19 pats. Premature discontinuations (no. of pats): progressive disease 9, cardiotoxicity 3, other toxicity 4, death 2, other reason 1. In 10 pats the dose of Myocet was reduced. The best response was scored for 50 pats with at least 1 measurable lesion: CR 4, PR 28, SD 14, PD 4. Mean LVEF in the entire group decreased during the study from 63 to 59 (9,2) %. The decrease in the AN pretreated group was 7% and in the not pretreated pats 3%. 4 pats met the LVEF criteria for cardiotoxicity and 3 others were withdrawn for cardiotoxicity without meeting the criteria. 6 of these pats were AN pretreated. None of them had signs/symptoms of HF. PR or better was observed in 64% of pats. Conclusion: Liposomal DOX might provide more cardiac safety compared to conventional AN, but pats pretreated with conventional AN seem to be more prone to LVEF decrease. No signs or symptoms of HF have been observed. The combination of Myocet® and docetaxel is efficacious and sufficiently well tolerated and is currently investigated in combination with trastuzumab in HER2 positive pats. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-16-13.