ay
Result†
Number of
Patients
Hazard Ratio DFS
(95% CI)
Number of
Patients
Hazard Ratio DFS
(95% CI)
IHC 3+
FISH (+)
FISH (−)
FISH Unknown
1170 0.42
(0.27, 0.64)
51 0.71
(0.04, 11.79)
51 0.69
(0.09, 5.14)
91
8
2258
0.56
(0.13, 2.50)
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)
* Median follow-up duration of 12.6 months in the one-year intravenous trastuzumab
treatment arm.
IHC by HercepTest, FISH by PathVysion (HER2/CEP17 ratio ≥ 2.0) as performedat a central laboratory.
All cases in this category in HERA were IHC 2+.
14.2 Metastatic Breast Cancer
Intravenous Trastuzumab
The safety and efficacy of intravenous trastuzumab in the treatment of women with metastatic breast cancer werestudied in a randomized, controlled clinical trial in combination with chemotherapy (H0648g, n=469 patients)and an open-label single agent clinical trial (H0649g, n=222 patients). Both trials studied patients with metastaticbreast cancer whose tumors overexpress the HER2 protein. Patients were eligible if they had level 2 or3 overexpression (based on a 0 to 3 scale) by immunohistochemical assessment of tumor tissue performed by acentral testing lab.
Previously Untreated Metastatic Breast Cancer (H0648g)
H0648g was a multicenter, randomized, open-label clinical trial conducted in 469 women with metastatic breastcancer who had not been previously treated with chemotherapy for metastatic disease. Patients were randomizedto receive chemotherapy alone or in combination with trastuzumab given intravenously as a 4 mg/kg loading dosefollowed by weekly doses of intravenous trastuzumab at 2 mg/kg. For those who had received prior anthracyclinetherapy in the adjuvant setting, chemotherapy consisted of paclitaxel (175 mg/m2 over 3 hours every 21 days forat least six cycles); for all other patients, chemotherapy consisted of anthracycline plus cyclophosphamide (AC:doxorubicin 60 mg/m2 or epirubicin 75 mg/m2 plus 600 mg/m2 cyclophosphamide every 21 days for six cycles).
Sixty-five percent of patients randomized to receive chemotherapy alone in this study received intravenoustrastuzumab at the time of disease progression as part of a separate extension study.
Based upon the determination by an Independent Response eva luation Committee, the patients randomized tointravenous trastuzumab and chemotherapy experienced a significantly longer time to disease progression, ahigher overall response rate (ORR), and a longer median duration of response as compared with patientsrandomized to chemotherapy alone. Patients randomized to intravenous trastuzumab and chemotherapy also hada longer median survival (see Table 11). These treatment effects were observed both in patients who receivedintravenous trastuzumab plus paclitaxel and in those who received intravenous trastuzumab plus AC; howeverthe magnitude of the effects was greater in the paclitaxel subgroup.
Table 11:
H0648g: Efficacy Results in First-Line Treatment for Metastatic Breast CancerCombined Results Paclitaxel Subgroup AC Subgroup
Intravenous
Trastuzumab
+ All Chemotherapy
(n=235)
All Chemotherapy
(n=234)
Intravenous
Trastuzumab
+ Paclitaxel
(n=92)
Paclitaxel
(n=96)
Intrav |
