LVEF
<50%
≥10%
decrease
≥16%
decrease <20% and ≥10% ≥20%
Studies 1 & 2b,c
AC→TH
(n = 1856)
23.1%
(428)
18.5%
(344)
11.2%
(208)
37.9%
(703)
8.9%
(166)
AC→T
(n = 1170)
11.7%
(137)
7.0%
(82)
3.0%
(35)
22.1%
(259)
3.4%
(40)
Study 3d
Trastuzumab
(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)
Study 4e
TCH
(n = 1056)
8.5%
(90)
5.9%
(62)
3.3%
(35)
34.5%
(364)
6.3%
(67)
AC→TH
(n = 1068)
17%
(182)
13.3%
(142)
9.8%
(105)
44.3%
(473)
13.2%
(141)
AC→T
(n = 1050)
9.5%
(100)
6.6%
(69)
3.3%
(35)
34%
(357)
5.5%
(58)
a For Studies 1, 2 and 3, events are counted from the beginning of trastuzumab treatment.
For Study 4, events are counted from the date of randomization.
b Studies 1 and 2 regimens: doxorubicin and cyclophosphamide followed by paclitaxel(AC→T) or paclitaxel plus trastuzumab (AC→TH). c Median duration of follow-up for Studies 1 and 2 combined was 8.3 years in the AC→THarm.
d Median follow-up duration of 12.6 months in the one-year trastuzumab treatment arm. e Study 4 regimens: doxorubicin and cyclophosphamide followed by docetaxel (AC→T) ordocetaxel plus trastuzumab (AC→TH); docetaxel and carboplatin plus trastuzumab(TCH).
Figure 1
Studies 1 and 2: Cumulative Incidence of Time to First LVEF Decline of ≥ 10 Percentage Points fromBaseline and to Below 50% with Death as a Competing Risk Event
Time 0 is initiation of paclitaxel or trastuzumab + paclitaxel therapy.
Figure 2
Study 3: Cumulative Incidence of Time to First LVEF Decline of ≥ 10 Percentage Points from Baseline and toBelow 50% with Death as a Competing Risk Event
Time 0 is the date of randomization.
Figure 3
Study 4: Cumulative Incidence of Time to First LVEF Decline of ≥10 Percentage Points from Baseline and toBelow 50% with Death as a Competing Risk Event
Time 0 is the date of randomization.
The incidence of treatment emergent congestive heart failure among patients in the metastatic breastcancer trials was classified for severity using the New York Heart Association classification system(I-IV, where IV is the most severe level of cardiac failure) (see Table 2). In the metastatic breast cancertrials, the probability of cardiac dysfunction was highest in patients who received trastuzumabconcurrently with anthracyclines.
In Study 7, 5.0% of patients in the trastuzumab plus chemotherapy arm compared to 1.1% of patients inthe chemotherapy alone arm had LVEF value below 50% with a ≥ 10% absolute decrease in LVEF frompretreatment values.
Infusion Reactions
During the first infusion with trastuzumab, the symptoms most commonly reported were chills and fever,occurring in approximately 40% of patients in clinical trials. Symptoms were treated with acetaminophen,diphenhydramine, and meperidine (with or without reduction in the rate of trastuzumab infusion);permanent discontinuation of trastuzumab for infusion reactions was required in < 1% of patients. Othersigns and/or symptoms may include nausea, vomiting, pain (in some cases at tumor sites), rigors, headache,dizziness, dyspnea, hy |
