static Breast Cancer
Among women receiving trastuzumab for treatment of metastatic breast cancer, the incidence of pulmonarytoxicity was also increased. Pulmonary adverse events have been reported in the post-marketing experience aspart of the symptom complex of infusion reactions. Pulmonary events include bronchospasm, hypoxia, dyspnea,pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, and acute respiratory distresssyndrome. For a detailed description, see Warnings and Precautions (5.4).
Thrombosis/Embolism
In 4 randomized, controlled clinical trials, the incidence of thrombotic adverse events was higher in patientsreceiving trastuzumab and chemotherapy compared to chemotherapy alone in three studies (2.6% vs. 1.5%[Study 1], 2.5% and 3.7% vs. 2.2% [Study 4] and 2.1% vs. 0% [Study 5]).
Diarrhea
Among women receiving adjuvant therapy for breast cancer, the incidence of NCI-CTC Grade 2 to 5 diarrhea(6.7% vs. 5.4% [Study 1]) and of NCI-CTC Grade 3 to 5 diarrhea (2.2% vs. 0% [Study 2]), and of Grade 1 to 4diarrhea (7% vs. 1% [Study 3; one-year trastuzumab treatment at 12.6 months median duration of follow-up])
were higher in patients receiving trastuzumab as compared to controls. In Study 4, the incidence of Grade 3 to 4diarrhea was higher [5.7% AC-TH, 5.5% TCH vs. 3.0% AC-T] and of Grade 1 to 4 was higher [51% AC-TH,63% TCH vs. 43% AC-T] among women receiving trastuzumab. Of patients receiving trastuzumab as a singleagent for the treatment of metastatic breast cancer, 25% experienced diarrhea. An increased incidence ofdiarrhea was observed in patients receiving trastuzumab in combination with chemotherapy for treatment ofmetastatic breast cancer.
Renal Toxicity
In Study 7 (metastatic gastric cancer) on the trastuzumab-containing arm as compared to the chemotherapyalone arm the incidence of renal impairment was 18% compared to 14.5%. Severe (Grade 3/4) renal failure was2.7% on the trastuzumab-containing arm compared to 1.7% on the chemotherapy only arm. Treatmentdiscontinuation for renal insufficiency/failure was 2% on the trastuzumab-containing arm and 0.3% on thechemotherapy only arm.
In the post-marketing setting, rare cases of nephrotic syndrome with pathologic evidence of glomerulopathyhave been reported. The time to onset ranged from 4 months to approximately 18 months from initiation oftrastuzumab therapy. Pathologic findings included membranous glomerulonephritis, focal glomerulosclerosis,and fibrillary glomerulonephritis. Complications included volume overload and congestive heart failure.
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 in the studies described below with the incidence ofantibodies in other studies or to other trastuzumab products may be misleading.
Among 903 women with metastatic breast cancer, human anti-human antibody (HAHA) to trastuzumab wasdetected in one patient using an enzyme-linked immunosorbent assay (ELISA). This patient did not experiencean allerg |
