2)
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, eventsare 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→TH arm.
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) or docetaxel 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 from Baselineand 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 breast cancertrials was classified for severity using the New York Heart Association classification system (I–IV, where IV isthe most severe level of cardiac failure) (see Table 2). In the metastatic breast cancer trials, the probability ofcardiac dysfunction was highest in patients who received trastuzumab concurrently with anthracyclines.
In Study 7, 5.0% of patients in the trastuzumab plus chemotherapy arm compared to 1.1% of patients in thechemotherapy 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); permanentdiscontinuation of trastuzumab for infusion reactions was required in < 1% of patients. Other signs and/orsymptoms may include nausea, vomiting, pain (in some cases at tumor sites), rigors, headache, dizziness,dyspnea, hypotension, elevated blood pressure, rash, and asthenia. Infusion reactions occurred in 21% and 35%of patients, and were severe in 1.4% and 9% of patients, on second or subsequent trastuzumab infusionsadministered as monotherapy or in combination with chemotherapy, respectively. In the post-marketing setting,severe infusion reactions, including hypersensitivity, anaphylaxis, and angioedema have been reported.
Anemia
In randomized controlled clinical trials, the overall incidence of anemia (30% vs. 21% [Study 5]), of selectedNCI-CTC Grade 2 to 5 anemia (12.3% vs. 6.7% [Study 1]), and of anemia requiring transfusions (0.1% vs.
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