n studied.
Table 1
Incidence of Congestive Heart Failure in Adjuvant Breast Cancer Studies
Incidence of CHF
Study Regimen Trastuzumab Control
1 & 2a
AC
b
→Paclitaxel+Trastuzumab 3.2% (64/2000)c 1.3% (21/1655)
3
d Chemo → Trastuzumab 2% (30/1678) 0.3% (5/1708)
4 AC
b
→ Docetaxel+Trastuzumab 2% (20/1068) 0.3% (3/1050)
4 Docetaxel+Carbo+Trastuzumab 0.4% (4/1056) 0.3% (3/1050)
a Median follow-up duration for Studies 1 and 2 combined was 8.3 years in the AC→TH arm.
b Anthracycline (doxorubicin) and cyclophosphamide.
c Includes 1 patient with fatal cardiomyopathy and 1 patient with sudden death without documented etiology.
d Includes NYHA II-IV and cardiac death at 12.6 months median duration of follow-up in the one-yeartrastuzumab arm.
In Study 3 (one-year trastuzumab treatment), at a median follow-up duration of 8 years, the incidence of severeCHF (NYHA III & IV) was 0.8%, and the rate of mild symptomatic and asymptomatic left ventriculardysfunction was 4.6%.
Table 2
Incidence of Cardiac Dysfunctiona in Metastatic Breast Cancer Studies
Study Event
Incidence
NYHA I-IV
Trastuzumab Control
NYHA III-IV
Trastuzumab Control
5 (AC)b Cardiac Dysfunction
5 (paclitaxel) Cardiac Dysfunction
6 Cardiac Dysfunctionc
28% 7%
11% 1%
7% N/A
19% 3%
4% 1%
5% N/A a Congestive heart failure or significant asymptomatic decrease in LVEF.
b Anthracycline (doxorubicin or epirubicin) and cyclophosphamide.
c Includes 1 patient with fatal cardiomyopathy.In Study 4, the incidence of NCI-CTC Grade 3/4 cardiac ischemia/infarction was higher in the trastuzumab
containing regimens (AC-TH: 0.3% (3/1068) and TCH: 0.2% (2/1056)) as compared to none in AC-T.
5.2 Infusion Reactions
Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion includednausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, andasthenia [see Adverse Reactions (6.1)].
In post-marketing reports, serious and fatal infusion reactions have been reported. Severe reactions, whichinclude bronchospasm, anaphylaxis, angioedema, hypoxia, and severe hypotension, were usually reportedduring or immediately following the initial infusion. However, the onset and clinical course were variable,including progressive worsening, initial improvement followed by clinical deterioration, or delayedpost-infusion events with rapid clinical deterioration. For fatal events, death occurred within hours to daysfollowing a serious infusion reaction.
Interrupt TRAZIMERA infusion in all patients experiencing dyspnea, clinically significant hypotension, andintervention of medical therapy administered (which may include epinephrine, corticosteroids,diphenhydramine, bronchodilators, and oxygen). Patients should be eva luated and carefully monitored untilcomplete resolution of signs and symptoms. Permanent discontinuation should be strongly considered in allpatients with severe infusion reactions.
There are no data regarding the most appropriate method of identification of patients who may safely beretreated with trastuzumab products after experiencing a severe infusion reaction. Prior to resumption oftrastuzumab infusion, the majority of patients who experienced a severe infusion reaction were pre-medicated
with antihistamines and/or cor |
