se reactions observed in clinical trials of adjuvant breast, metastatic breast cancer, metastatic gastric cancer, or post‑marketing experience.
Cardiomyopathy
Serial measurement of cardiac function (LVEF) was obtained in clinical trials in the adjuvant treatment of breast cancer. In Study 3, the median duration of follow‑up was 12.6 months (12.4months in the observation arm; 12.6months in the 1‑year Herceptin arm); and in Studies 1 and 2, 23months in the AC‑T arm, 24months in the AC‑TH arm. In Studies 1 and 2, 6% of patients were not permitted to initiate Herceptin following completion of AC chemotherapy due to cardiac dysfunction (LVEF < 50% or ≥ 15point decline in LVEF from baseline to end of AC). Following initiation of Herceptin therapy, the incidence of new‑onset dose‑limiting myocardial dysfunction was higher among patients receiving Herceptin and paclitaxel as compared to those receiving paclitaxel alone in Studies 1 and 2, and in patients receiving Herceptin monotherapy compared to observation in Study 3 (see Table 6, Figures 1 and 2).
Table 6*: Per‑patient Incidence of New Onset Myocardial Dysfunction (by LVEF) Studies1, 2, 3 and 4
|
|
LVEF <50%
and Absolute Decrease from Baseline |
Absolute LVEF Decrease |
|
|
LVEF <50% |
≥10% decrease |
≥16% decrease |
<20% and ≥10% |
≥20% |
|
|
|
Studies1 & 2† |
|
|
|
|
|
AC→TH
(n=1606) |
22.8%
(366) |
18.3%
(294) |
11.7%
(188) |
33.4%
(536) |
9.2%
(148) |
AC→T
(n=1488) |
9.1%
(136) |
5.4%
(81) |
2.2%
(33) |
18.3%
(272) |
2.4%
(36) |
|
Study3 |
|
|
|
|
|
Herceptin
(n=1678) |
8.6%
(144) |
7.0%
(118) |
3.8%
(64) |
22.4%
(376) |
3.5%
(59) |
Observation
(n=1708) |
2.7%
(46) |
2.0%
(35) |
1.2%
(20) |
11.9%
(204) |
1.2%
(21) |
|
Study4 ‡ |
|
|
|
|
|
TCH
(n=1056) |
8.5%
(90) |
5.9%
(62) |
