Cardiac tolerability of trastuzumab in metastatic breast cancer (MBC) patients previously treated with high-dose chemotherapy (HDC) with autologous hemopoietic support: Retrospective analysis from Gruppo Italiano Trapianto Midollo Osseo (GITMO) Solid Tumor Working Party

Abstract

10558 Background: HER-2 overexpression is associated to a poor prognosis in high-risk and MBC patients treated with HDC. HER-2 status is also a predictive factor of response to trastuzumab: when trastuzumab is administered in combination with or sequentially to chemotherapy, a significant DFS and/or survival improvement has been observed in HER2+ early and MBC. Unfortunately, in both settings, trastuzumab was associated with an increased risk of cardiac dysfunctions (CD). Patients and Methods: In order to evaluate the cardiac safety of trastuzumab after HDC, we have reviewed the clinical charts of HER2-overexpressing MBC patients treated with HDC and trastuzumab at 11 centres of the GITMO group. Age, baseline LVEF, radiation therapy on cardiac area, exposure to anthracycline, single or multiple transplant, high-dose agents, trastuzumab treatment duration were recorded as potential risk factors. Cardiac dysfunction (CD) was defined as: 1) decline of LVEF ≥ 10% to below 50%, 2) decline of LVEF between 5 and 9% to below 50% with symptomatic (NYHA class III-IV) congestive heart failure (CHF), 3) any symptomatic CHF event. Results: Fifty-three patients treated between 1999 and 2005 have been included in the analysis. Median age was 47 years (range 29–66). Median interval between HDC and trastuzumab was 6 months. Median LVEF at baseline was 60.5%; at the end of trastuzumab (data available for 28 patients only) it was 55% (p = 0.01). Five out of the 28 (17.9%) pts experienced CD. Two out of 53 (3.8%) pts developed a symptomatic (NYHA class III) CHF. Age ≥ 50 years was the only factor significantly associated with CD. However age ≥ 50 years and multiple transplant procedure were associated with a significant decline of LVEF (p: 0.02). Conclusion: The incidence of CD is not superior to that reported with trastuzumab after standard chemotherapy. However pts with age ≥ 50 years or receiving multiple course of HDC, should be considered at risk for CD. No significant financial relationships to disclose.