TrastuzumabArm (H0648g and H0649g)
Single agent*
n = 352
Intravenous
trastuzumab
+ paclitaxel
n = 91
Paclitaxel
Alone
n = 95
Intravenous
trastuzumab
+ AC†
n = 143
AC† Alone
n = 135
Nervous
Insomnia 14% 25% 13% 29% 15%
Dizziness 13% 22% 24% 24% 18%
Paresthesia 9% 48% 39% 17% 11%
Depression 6% 12% 13% 20% 12%
Peripheral neuritis 2% 23% 16% 2% 2%
Neuropathy 1% 13% 5% 4% 4%
Respiratory
Cough increased 26% 41% 22% 43% 29%
Dyspnea 22% 27% 26% 42% 25%
Rhinitis 14% 22% 5% 22% 16%
Pharyngitis 12% 22% 14% 30% 18%
Sinusitis 9% 21% 7% 13% 6%
Skin
Rash 18% 38% 18% 27% 17%
Herpes simplex 2% 12% 3% 7% 9%
Acne 2% 11% 3% 3% < 1%
Urogenital
Urinary tract infection 5% 18% 14% 13% 7% * Data for intravenous trastuzumab single agent were from 4 studies, including 213 patients fromH0649g.
Anthracycline (doxorubicin or epirubicin) and cyclophosphamide.
6.2 Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation ishighly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody(including neutralizing antibody) positivity in an assay may be influenced by several factors including assaymethodology, sample handling, timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies to HERCEPTIN HYLECTA and intravenoustrastuzumab in the study described below with the incidence of antibodies in other studies or to other productsmay be misleading.
In the HannaH study, at a median follow-up exceeding 60 months, the incidence of treatment-induced/enhancedanti-trastuzumab antibodies was 10% (30/296) in patients treated with intravenous trastuzumab and 16% (47/295)in patients receiving HERCEPTIN HYLECTA. Neutralizing anti-trastuzumab antibodies were detected in postbaseline
samples in 2/30 patients in the intravenous trastuzumab arm and 3/47 patients in the HERCEPTINHYLECTA arm. The incidence of treatment-induced/enhanced anti-recombinant human hyaluronidase antibodieswas 21% (62/295) in the HERCEPTIN HYLECTA arm. None of the patients who tested positive for antirecombinanthuman hyaluronidase antibodies tested positive for neutralizing antibodies.
The clinical relevance of the development of anti-trastuzumab or anti-recombinant human hyaluronidaseantibodies after treatment with HERCEPTIN HYLECTA is not known.
6.3 Postmarketing Experience
The following adverse reactions have been identified during post-approval use of trastuzumab. Because thesereactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimatetheir frequency or establish a causal relationship to drug exposure.
•Administration-related reaction [see Warnings and Precautions (5.5)]
•Oligohydramnios or oligohydramnios sequence, including pulmonary hypoplasia, skeletal abnormalities,and neonatal death [see Warnings and Precautions (5.2)]
•Glomerulopathy [see Adverse Reactions (6.1)]
•Immune thrombocytopenia
•Tumor lysis syndrome (TLS): Cases of possible TLS have been reported in patients treated withtrastuzumab. Patients with significant tumor burden (e.g. bulky metastases) may be at a higher risk. Patientscould present with hyperuricemia, hyperphos |
