ction has not been
studied.
Patients who receive anthracycline after stopping HERCEPTIN HYLECTA may also be at increased risk ofcardiac dysfunction [see Drug Interactions (7) and Clinical Pharmacology (12.3)].
Cardiac Monitoring
Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF byechocardiogram or MUGA scan. The following schedule is recommended:
•Baseline LVEF measurement immediately prior to initiation of HERCEPTIN HYLECTA
•LVEF measurements every 3 months during and upon completion of HERCEPTIN HYLECTA
•Repeat LVEF measurement at 4 week intervals if HERCEPTIN HYLECTA is withheld for significantleft ventricular cardiac dysfunction [see Dosage and Administration (2.3)]
•LVEF measurements every 6 months for at least 2 years following completion of HERCEPTINHYLECTA as a component of adjuvant therapy.
HERCEPTIN HYLECTA
In the HannaH study, the overall percentage of patients with at least one cardiac disorder was similar in both studyarms: 15% (44/297) of patients in the HERCEPTIN HYLECTA arm and 14% (42/298) of patients in theintravenous trastuzumab arm. The most frequent cardiac adverse reactions were left ventricular dysfunction [3.4%
(10/297) and 4.0% (12/298)], tachycardia [2% (6/297) and 3% (9/298)] and palpitations [2% (6/297) and 1.3%(4/298)] in the HERCEPTIN HYLECTA arm and the intravenous trastuzumab arm, respectively. The incidenceof cardiac failure and congestive cardiac failure was 1% (3/297) in the HERCEPTIN HYLECTA arm and <1%(1/298) in the intravenous trastuzumab arm. The proportion of patients in each treatment arm with a significantdecrease in LVEF defined as a drop of ≥10% points to a LVEF of <50% was comparable between treatment arms[3.8% (11/297) in the HERCEPTIN HYLECTA arm and 4.2% (12/298) in the intravenous trastuzumab arm]. Inpatients with lower body weights (<59 kg, the lowest body weight quartile) the fixed-dose used in theHERCEPTIN HYLECTA arm was not associated with an increased risk of cardiac events or significant drop inLVEF.
In the SafeHER study, in patients treated with HERCEPTIN HYLECTA, 17% (323/1864) reported a cardiacdisorder during the treatment period. Decreased ejection fraction, reported in 4.5% (84/1864) of the patients wasthe most frequently reported cardiac disorder. Congestive cardiac failure was reported in <1% (10/1864) of
patients and <1% (4/1864) of patients reported cardiac failure during the treatment period. One patient reportedcongestive cardiac failure during the follow-up period. Six percent (111/1864) of the patients treated withHERCEPTIN HYLECTA had an LVEF <50% with a decrease of ≥10 points in LVEF from baseline.
Trastuzumab (intravenous formulation):
In study NSABP B31 (NCT00004067), 15% (158/1031) of patients discontinued intravenous trastuzumab dueto clinical evidence of myocardial dysfunction or significant decline in LVEF after a median follow-up durationof 8.7 years in the AC-TH arm. In the HERA study (one-year intravenous trastuzumab treatment;NCT00045032), the number of patients who discontinued intravenous trastuzumab due to cardiac toxicity at12.6 months median duration of follow-up was 2.6% (44/1678). In the BCIRG006 study (NCT00021255), atotal of 2.9% (31/1056) of patients in the TCH arm (1.5% during the chemotherapy phase and 1.4% during themonotherapy phase) and 5.7% (61/1068) of patients in the AC-TH arm (1.5 |
