vant Treatment of Breast Cancer (Studies1 and 2)
Figure 5
Duration of Disease‑Free Survival in Patients with Adjuvant Treatment of Breast Cancer (Study4)
Exploratory analyses of DFS as a function of HER2 overexpression or gene amplification were conducted for patients in Studies2 and 3, where central laboratory testing data were available. The results are shown in Table8. The number of events in Study2 was small with the exception of the IHC3+/FISH+ subgroup, which constituted 81% of those with data. Definitive conclusions cannot be drawn regarding efficacy within other subgroups due to the small number of events. The number of events in Study3 was adequate to demonstrate significant effects on DFS in the IHC3+/FISH unknown and the FISH+/IHC unknown subgroups.
Table 8: Treatment Outcomes in Studies2 and 3 as a Function of HER2 Overexpression or Amplification
|
|
Study 2 |
Study 3 |
|
HER2 Assay Result* |
Number of Patients |
Hazard Ratio DFS (95%CI) |
Number of Patients |
Hazard Ratio DFS (95%CI) |
|
|
|
IHC 3+ |
|
FISH (+) |
1170 |
0.42
(0.27, 0.64) |
91 |
0.56
(0.13, 2.50) |
|
FISH (−) |
51 |
0.71
(0.04, 11.79) |
8 |
— |
|
FISH Unknown |
51 |
0.69
(0.09, 5.14) |
2258 |
0.53
(0.41, 0.69) |
IHC < 3+ /
FISH(+) |
174 |
1.01
(0.18, 5.65) |
299† |
0.53
(0.20, 1.42) |
|
IHC unknown / FISH(+) |
— |
— |
724 |
0.59
(0.38, 0.93) |
14.2 Metastatic Breast Cancer
The safety and efficacy of Herceptin in treatment of women with metastatic breast cancer were studied in a randomized, controlled clinical trial in combination with chemotherapy (Study 5, n=469 patients) and an open‑label single agent clinical trial (Study 6, n=222 patients). Both trials studied patients with metastatic breast cancer whose tumors overexpress the HER2 protein. Patients were eligible if they had 2 or 3 levels of overexpression (based on a 0 to 3 scale) by immunohistochemical assessment of tumor tissue performed by a central testing lab.
Previously Untreated Metastatic Breast Cancer (Study 5)
Study 5 was a multicenter, randomized, open‑label clinical trial conducted in 469women with metastatic breast cancer who had not been previously treated with chemotherapy for metastatic disease. Tumor specimens were tested by IHC (Clinical Trial Assay, CTA) and scored as 0, 1+, 2+, or 3+, with 3+ indicating the strongest positivity. Only patients with 2+ or 3+ positive tumors were eligible (about 33% of those screened). Patients were randomized to receive chemotherapy alone or in combination with Herceptin given intravenously as a 4mg/kg loading dose followed by weekly doses of Herceptin at 2mg/kg. Fo
