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KANJINTI(trastuzumab-anns)for injection, for intravenous useInitial U.S.(二十五)
); 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 trastuzumab 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 totrastuzumab and chemotherapy experienced a significantly longer median 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 trastuzumab and chemotherapy also had a longermedian survival (see Table 11). These treatment effects were observed both in patients who receivedtrastuzumab plus paclitaxel and in those who received trastuzumab plus AC; however the magnitude of theeffects was greater in the paclitaxel subgroup.
Table 11
Study 5: Efficacy Results in First-Line Treatment for Metastatic Breast CancerCombined Results Paclitaxel Subgroup AC Subgroup
Trastuzumab +
All Chemo- All Chemotherapy
therapy
(n = 235) (n = 234)
Trastuzumab +
Paclitaxel Paclitaxel
(n = 92) (n = 96)
Trastuzumab +
ACa
(n = 143)
AC
(n = 138)
Primary Endpoint
Median 7.2 4.5 6.7 2.5 7.6 5.7
TTP (mos)b,c
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 45 29 38 15 50 38
Response
Rateb
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 8.3 5.8 8.3 4.3 8.4 6.4
(mos)b,c
25%, 75% 6, 15 4, 8 5, 11 4, 7 6, 15 4, 8
Quartile
Med Survival 25.1 20.3 22.1 18.4 26.8 21.4
(mos)c
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 thehighest 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+
FISH (+)a
FISH ()
a
CTA 2+
FISH (+)
FISH (+)
CTA 3+
FISH (+)
FISH ()
469
325
126
120
32
83
349
293
43
0.49 (0.40, 0.61)
0.44 (0.34, 0.57)
0.62 (0.42, 0.94)
0.76 (0.50, 1.15)
0.54 (0.21, 1.35)
0.77 (0.48, 1.25)
0.42 (0.33, 0.54)
0.42 (0.32, 0.55)
0.43 (0.20, 0.94)
0.80 (0.64, 1.00)
0.70 (0.53, 0.91)
1.06 (0.70, 1.63)
1.26 (0.82, 1.94)
1.31 (0.53, 3.27)
1.11 (0.68, 1.82)
0.70 (0.51, 0.90)
0.67 (0.51, 0.89)
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 pluschemotherapy arm versus the chemotherapy arm.
Previously Treated Metastatic Breast Cancer (Study 6)
Trastuzumab was studied as a si |
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