enous
Trastuzumab
+ AC *
(n=143)
AC
(n=138)
Primary Endpoint
Median
TTP (mos) †,‡
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-value § < 0.0001 < 0.0001 0.002
Secondary Endpoints
Overall Response
Rate †
45 29 38 15 50 38
95% CI 39, 51 23, 35 28, 48 8, 22 42, 58 30, 46
p-value < 0.001 < 0.001 0.10
Median Resp
Duration (mos) †,‡ 8.3 5.8 8.3 4.3 8.4 6.4
25%, 75%
Quartile
Med Survival
(mos) ‡
6, 15
25.1
4, 8
20.3
5, 11
22.1
4, 7
18.4
6, 15
26.8
4, 8
21.4
95% CI 22, 30 17, 24 17, 29 13, 24 23, 33 18, 27
p-value § 0.05 0.17 0.16
* AC=Anthracycline (doxorubicin or epirubicin) and cyclophosphamide.
† Assessed by an independent Response eva luation Committee.
‡ Kaplan-Meier Estimate.
§ log-rank test. χ2-test.
Data from H0648g suggest that the beneficial treatment effects were largely limited to patients with the highestlevel of HER2 protein overexpression (3+) (see Table 12).
Table 12:
Treatment Effects in H0648g as a Function of HER2 Overexpression orAmplification
HER2 Assay
Result
Number of
Patients
(N)
Relative Risk * for Time to
Disease Progression
(95% CI)
Relative Risk * for Mortality
(95% CI)
CTA 2+ or 3+
FISH (+) †
FISH (−) †
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)
*
The relative risk represents the risk of progression or death in the trastuzumab pluschemotherapy arm versus the chemotherapy arm.
FISH testing results were available for 451 of the 469 patients enrolled on study.
Previously Treated Metastatic Breast Cancer (Study H0649g)
Intravenous trastuzumab was studied as a single agent in a multicenter, open-label, single-arm clinical trial (StudyH0649g) in patients with HER2 overexpressing MBCwho had relapsed following one or two prior chemotherapyregimens 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% had received priormyeloablative treatment with hematopoietic rescue. Patients were treated with a loading dose of 4 mg/kg IVfollowed 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 in patientswhose tumors tested as CTA 3+ was 18% while in those that tested as CTA 2+, it was 6%.
14.3 Patient Experience
The PrefHER study (NCT01401166) was a randomized, multi-center, two-arm, cross-over trial conducted in240 patients with HER2-positive breast cancer undergoing neoadjuvant or adjuvant treatment. One hundredtwenty-one patients in arm A rec |
