Publication Year: 2000 Visited: 187

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Final Report: Weekly (W) Herceptin (H) and Taxol (T) for Metastatic Breast Cancer (MBC): Analysis of Efficacy by HER2 Immunophenotype [Immunohistochemistry (IHC)] and Gene Amplification [Fluorescent in-Situ Hybridization (FISH)]. A D Seidman, M Fornier, F Esteva, L Tan, S Kaptain, A Bach, C D Arroyo, V Currie, T Gilewski, M Theodoulou, M E Moynahan, M Moasser, G D'Andrea, N Sklarin, M Dickler, J Chin, C Denton, D Bacotti, J Willey, D Frye, G Hortobagyi, L Norton, C Hudis, Memorial Sloan-Kettering Cancer Ctr, New York, NY; M D Anderson Cancer Ctr, Houston, TX.

An overall survival advantage is gained by the addition of W H to T (q 3 W) for first-line therapy of HER2 overexpressing MBC (Norton et al. Proc ASCO '99). We treated 94 pts with W T (1-hr) + H: W T at 90 mg/m² and W H 4 mg/kg loading dose (90 min. i.v.), then 2 mg/kg (30 min. i.v.). Median (M) age: 51 yrs (28-68), M KPS: 90% (70-100), M organ systems with MBC: 2 (1-4); 80% had visceral-dominant disease. M no. prior regimens: 1 (0-3); prior adjuvant rx: 59%, prior anthracycline: 66%, prior T (>1yr): 13%. 2,108 infusions have been given, M 33/pt (1-73). M T delivered dose intensity to date is 82 mg/m² /wk (52-90). Neuropathy was the major dose-limiting adverse event (10% grade 3, 1% grade 4). Grade 3/4 neutropenia: 14% of patients, with 3 episodes of febrile neutropenia. Serial ventriculography through 16 mos. shows 2 pts. with decline in LVEF >15%. 1 pt. had CHF, and 1 had myocardial infarction w/o CHF. For 82 evaluable patients 45 (55%) had tumoral HER2 overexpression by DAKO HercepTest™, 54 (66%) by p-Ab1, 31 (38%) by TAB-250, and 35 (43%) by CB-11. 30 of 65 evaluable pts (46%) had HER2 gene amplification by FISH (Vysis, PathVysion;™). Comparisons of HER2 status between the 4 different IHC antibodies (2 polyclonal, and 2 monoclonal) and FISH will be presented. The overall response rate was 59% (95% Cl 49-69%) (3% CR), with a M response duration of 6 months (2-19+). Response rates for DAKO +: 62% (95% Cl 48-76%), p-Ab1 +: 59% (46-72%), TAB-250 +: 81% (67-95%), CB-11+: 74% (60-89%), FISH +: 70% (54-86%). H is incorporated into CALGB 9840, where randomization to W T+H vs. q 3W T + W H for HER2 overexpressors is planned, and to H vs. no H for non-overexpressors. In addition, W T+H will be evaluated as a component of adjuvant therapy for node+/HER2+ resected breast cancer in Intergroup trial N-9831. Support: Genentech, Inc.