% during the chemotherapy phaseand 4.2% during the monotherapy phase) discontinued intravenous trastuzumab due to cardiac toxicity.
Among 64 patients receiving adjuvant chemotherapy (studies NSABP B31 and NCCTG N9831;NCT00005970) who developed congestive heart failure (CHF), one patient died of cardiomyopathy, one patientdied suddenly without documented etiology, and 33 patients were receiving cardiac medication at lastfollow-up. Approximately 24% of the surviving patients had recovery to a normal LVEF (defined as ≥ 50%)and no symptoms on continuing medical management at the time of last follow-up. Incidence of CHF is presented in Table 1. The safety of continuation or resumption of intravenous trastuzumab in patients withtrastuzumab-induced left ventricular cardiac dysfunction has not been studied.
Table 1
Incidence of Congestive Heart Failure in Adjuvant Breast Cancer Studies
Incidence of CHF
Study Regimen Intravenous Trastuzumab Control
NSABP B31 & AC†
→paclitaxel + intravenous 3.2% (64/2000) ‡ 1.3% (21/1655)
NCCTG N9831* trastuzumab
HERA§ Chemo → intravenous trastuzumab 2% (30/1678) 0.3% (5/1708)
BCIRG006 AC†
→docetaxel + intravenous 2% (20/1068) 0.3% (3/1050)
trastuzumab
BCIRG006 Docetaxel + carboplatin + 0.4% (4/1056) 0.3% (3/1050)
intravenous trastuzumab
* Median follow-up duration for studies NSABP B31 and NCCTG N9831combined was 8.3 years in the AC→THarm.
Anthracycline (doxorubicin) and cyclophosphamide.
Includes 1 patient with fatal cardiomyopathy and 1 patient with sudden death without documented etiology.
Includes NYHA II-IV and cardiac death at 12.6 months median duration of follow-up in the one-year intravenoustrastuzumab arm.In the HERA study (one-year intravenous trastuzumab treatment), at a median follow-up duration of 8 years, theincidence of severe 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 Dysfunction* in Metastatic Breast Cancer Studies
Incidence
NYHA I−IV NYHA III−IV
Intravenous Intravenous
Study Event Trastuzumab Control Trastuzumab Control
H0648g
(AC)† Cardiac Dysfunction 28% 7% 19% 3%
H0648g
(paclitaxel) Cardiac Dysfunction 11% 1% 4% 1%
H0649g Cardiac Dysfunction‡ 7% N/A 5% N/A
* Congestive heart failure or significant asymptomatic decrease in LVEF.
Anthracycline (doxorubicin or epirubicin) and cyclophosphamide.
Includes 1 patient with fatal cardiomyopathy.
In the BCIRG006 study, the incidence of NCI-CTC Grade 3/4 cardiac ischemia/infarction was higher in theintravenous trastuzumab containing regimens [AC-TH: 0.3% (3/1068) and TCH: 0.2% (2/1056)] as compared
to none in AC-T.
5.2 Embryo-Fetal Toxicity
HERCEPTIN HYLECTA can cause fetal harm when administered to a pregnant woman. In post-marketingreports, use of trastuzumab during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequencemanifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.
Verify the pregnancy status of females of reproductive potential prior to the initiation of HERCEPTINHYLECTA. Advise pregnant women and females of reproductive potential that exposure to HERCEPTINHYLECTA during pregnancy or within 7 months prior to conception can result in fetal harm. Advise |
