% (21/1655)
3d Chemo → Trastuzumab 2% (30/1678) 0.3% (5/1708)
4 ACb
→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 documentedetiology.
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 ofsevere CHF (NYHA III & IV) was 0.8%, and the rate of mild symptomatic and asymptomatic leftventricular dysfunction was 4.6%.
Table 2
Incidence of Cardiac Dysfunctiona
in Metastatic Breast Cancer Studies
Incidence
NYHA I-IV NYHA III-IV
Study Event Trastuzumab Control Trastuzumab Control
5
(AC)b
Cardiac Dysfunction 28% 7% 19% 3%
5
(paclitaxel)
Cardiac Dysfunction 11% 1% 4% 1%
6 Cardiac Dysfunctionc 7% N/A 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 nonein AC-T.
5.2 Infusion Reactions
Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasionincluded nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension,rash, and asthenia [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 KANJINTI 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-medicatedwith antihistamines and/or corticosteroids. While some patients tolerated trastuzumab infusions, others hadrecurrent severe infusion reactions despite pre-medications.
5.3 Embryo-Fetal Toxicity
Trastuzumab products can cause fetal harm when administe |
