USA. Genentech Inc. has issued a ´Dear Health-care Provider' letter to advise that the addition of trastuzumab (Herceptin) to chemotherapy has been associated with increased cardiotoxicity compared with chemotherapy alone in a recent study. In the letter, Genentech presents results from a preliminary analysis of safety data from a Phase III trial, in which 2043 women with operable, human epidermal growth factor receptor 2 (HER2)-over-expressing breast cancer were randomized to receive trastuzumab (Herceptin) in addition to chemotherapy (n = 1019) or chemotherapy alone (*). Among the evaluable patients with adequate heart function who were able to receive trastuzumab (Herceptin), 30.5% had ≥ 1 dose delay because of asymptomatic Left Ventricular Ejection Fraction (LVEF) decrease or heart disorders, and trastuzumab (Herceptin) was discontinued before completion of therapy because of an asymptomatic LVEF decrease in 14.3%, or because of other heart disorders in 4.3%. The 3-year cumulative incidence of New York Heart Association Class III and IV congestive heart failure and cardiac death was significantly increased in the trastuzumab (Herceptin) group compared with the chemotherapy alone group (4.1% vs 0.8%). One cardiac death was reported in the control group, but none were reported in the trastuzumab (Herceptin) group. The company also reports that a final analysis of the cardiac safety data is ongoing.
(*National Surgical Adjuvant Breast and Bowel Project study B-31. Treatment consisted of doxorubicin and cyclophosphamide (4 cycles) followed by paclitaxel every three weeks (4 cycles). Patients in the trastuzumab (Herceptin) group received the drug at the approved dose and schedule for one year, during and following paclitaxel).
'Dear Health-care Provider' letter from Genentech Inc., August 2005 (http://www.fda.gov).