Publication Year: 2000 Visited: 313

275

First-Line, Non-Hormonal, Treatment of Women with HER2 Overexpressing Metastatic Breast Cancer with Herceptin (Trastuzumab, Humanized Anti-HER2 Antibody). C. Vogel, M. Cobleigh, D. Tripathy, L. Harris, L. Fehrenbacher, D. Slamon, M. Ash, W. Novotny, S. Stewart, S. Shak, Aventura Comp Cancer Ctr, Aventura, FL.

Herceptin, a new targeted antineoplastic agent, has been shown to improve outcomes for women with metastatic breast cancer (MBC) when used with chemotherapy (CT) in a first treatment for MBC or as a single agent for MBC progressing after initial CT. This study examined the usefulness of Herceptin alone, in lieu of first CT, in women with MBC. 114 women with HER2 overexpressing tumors were randomized to a standard lower dose regimen of Herceptin (LDG) - 4 mg/kg IV loading and 2 mg/kg IV weekly until progression - or a higher dose regimen (HDG) - 8 mg/kg IV loading and 4 mg/kg IV weekly until progression. Mean age was 54 years. 50% of patients were postmenopausal. 76% of patients had tumors expressing HER2 at the 3+ level. 44% and 39% of patients had lung or liver involvement, respectively. Median disease free interval was 17 months. 51% of patients had received adjuvant anthracyclines. 13% of patients had undergone adjuvant transplantation. The response rate for the entire group was 26%. Response rates in the two dosage groups were similar: 25% (95% CI - 14.3, 36.5) in the LDG and 27% (15.5, 39.0) in the HDG. A number of patients demonstrated long term stability of disease (> 6 months) (LTSD). The clinical benefit rates (CR+PR+LTSD) were also similar: 36% in the LDG and 40% in the HDG. All responders had tumors that overexpressed HER2 at the 3+ level. Median times to disease progression were similar: 3.5 months (3.3, 5.1) for the LDG and 3.8 months (2.4, 5.5) for the HDG. Overall survivals were also similar: 22.9 months (16.0, 37.1) for the LDG and 25.8 months (13.3, 34.7) for the HDG. An infusion-related symptom complex of chills, fever, and pain was again noted, particularly with first infusion. There was a suggestion of a dose effect with higher rates of certain adverse events in the HDG. Only two patients were determined independently to have developed cardiac dysfunction. Both had significant underlying ischemic cardiac disease. Herceptin alone is an effective and safe treatment for patients with recently diagnosed MBC. Survivals in this study were similar to those reported with first line Herceptin plus CT.