|
TRAZIMERA(trastuzumab-qyyp)for injection, for intravenous us(二十五)
who received trastuzumab plus paclitaxeland in those who received trastuzumab plus AC; however the magnitude of the effects was greater in thepaclitaxel subgroup.
Table 11
Study 5: Efficacy Results in First-Line Treatment for Metastatic Breast CancerCombined Results Paclitaxel Subgroup AC Subgroup
Trastuzumab +
All
Chemotherapy
(n = 235)
All
Chemotherapy
(n = 234)
Trastuzumab +
Paclitaxel
(n = 92)
Paclitaxel
(n = 96)
Trastuzumab
+ ACa
(n = 143)
AC
(n = 138)
Primary Endpoint
Median
TTP
(mos)b,c
7.2 4.5 6.7 2.5 7.6 5.7
95% CI 7, 8 4, 5 5, 10 2, 4 7, 9 5, 7
p-valued < 0.0001 < 0.0001 0.002
Secondary Endpoints
Overall
Response
Rateb
45 29 38 15 50 38
95% CI 39, 51 23, 35 28, 48 8, 22 42, 58 30, 46
p-valuee < 0.001 < 0.001 0.10
Median
Resp
Duration
(mos)b,c
8.3 5.8 8.3 4.3 8.4 6.4
25%,
75%
Quartile
6, 15 4, 8 5, 11 4, 7 6, 15 4, 8
Med
Survival
(mos)c
25.1 20.3 22.1 18.4 26.8 21.4
95% CI 22, 30 17, 24 17, 29 13, 24 23, 33 18, 27
p-valued 0.05 0.17 0.16 a AC = Anthracycline (doxorubicin or epirubicin) and cyclophosphamide.
b Assessed by an independent Response eva luation Committee.
c Kaplan-Meier Estimate.
d log-rank test.e χ2-test.
Data from Study 5 suggest that the beneficial treatment effects were largely limited to patients with the highest
level of HER2 protein overexpression (3+) (see Table 12).
Table 12
Treatment Effects in Study 5 as a Function of HER2 Overexpression or Amplification
HER2 Assay
Result
Number of
Patients
(N)
Relative Riskb for Time to Disease
Progression
(95% CI)
Relative Riskb for
Mortality
(95% CI)
CTA 2+ or 3+ 469 0.49 (0.40, 0.61) 0.80 (0.64, 1.00)
FISH (+)a 325 0.44 (0.34, 0.57) 0.70 (0.53, 0.91)
FISH (−)a 126 0.62 (0.42, 0.94) 1.06 (0.70, 1.63)
CTA 2+ 120 0.76 (0.50, 1.15) 1.26 (0.82, 1.94)
FISH (+) 32 0.54 (0.21, 1.35) 1.31 (0.53, 3.27)
FISH (–) 83 0.77 (0.48, 1.25) 1.11 (0.68, 1.82)
CTA 3+ 349 0.42 (0.33, 0.54) 0.70 (0.51, 0.90)
FISH (+) 293 0.42 (0.32, 0.55) 0.67 (0.51, 0.89)
FISH (–) 43 0.43 (0.20, 0.94) 0.88 (0.39, 1.98)
a FISH testing results were available for 451 of the 469 patients enrolled on study.
b The relative risk represents the risk of progression or death in the trastuzumab plus chemotherapy armversus the chemotherapy arm.
Previously Treated Metastatic Breast Cancer (Study 6)
Trastuzumab was studied as a single agent in a multicenter, open-label, single-arm clinical trial (Study 6) inpatients with HER2 overexpressing metastatic breast cancer who had relapsed following one or two priorchemotherapy regimens for metastatic disease. Of 222 patients enrolled, 66% had received prior adjuvant
chemotherapy, 68% had received two prior chemotherapy regimens for metastatic disease, and 25% hadreceived prior myeloablative treatment with hematopoietic rescue. Patients were treated with a loading dose of4 mg/kg IV followed by weekly doses of trastuzumab at 2 mg/kg IV.
The ORR (complete response + partial response), as determined by an independent Response eva luationCommittee, was 14%, with a 2% complete response rate and a 12% partial response rate. Complete responseswere observed only in patients with disease limited to skin and lymph nodes. The overall response rate inpatients whose tumors tested as CTA 3+ was 18% while in those that tested as CTA 2+, it was 6%.
14.3 Metastatic Gastric |
|
