potension, elevated blood pressure, rash, and asthenia. Infusion reactions occurredin 21% and 35% of patients, and were severe in 1.4% and 9% of patients, on second or subsequenttrastuzumab infusions administered as monotherapy or in combination with chemotherapy, respectively.
In the post-marketing setting, severe infusion reactions, including hypersensitivity, anaphylaxis, andangioedema have been reported.
Anemia
In randomized controlled clinical trials, the overall incidence of anemia (30% vs. 21% [Study 5]), ofselected NCI-CTC Grade 2–5 anemia (12.3% vs. 6.7% [Study 1]), and of anemia requiring transfusions(0.1% vs. 0 patients [Study 2]) were increased in patients receiving trastuzumab and chemotherapycompared with those receiving chemotherapy alone. Following the administration of trastuzumab as asingle agent (Study 6), the incidence of NCI-CTC Grade 3 anemia was < 1%. In Study 7 (metastatic gastriccancer), on the trastuzumab containing arm as compared to the chemotherapy alone arm, the overallincidence of anemia was 28% compared to 21% and of NCI-CTC Grade 3/4 anemia was 12.2% comparedto 10.3%.
Neutropenia
In randomized controlled clinical trials in the adjuvant setting, the incidence of selected NCI-CTC Grade4–5 neutropenia (1.7% vs. 0.8% [Study 2]) and of selected Grade 2–5 neutropenia (6.4% vs. 4.3% [Study1]) were increased in patients receiving trastuzumab and chemotherapy compared with those receivingchemotherapy alone. In a randomized, controlled trial in patients with metastatic breast cancer, theincidences of NCI-CTC Grade 3/4 neutropenia (32% vs. 22%) and of febrile neutropenia (23% vs. 17%)were also increased in patients randomized to trastuzumab in combination with myelosuppressivechemotherapy as compared to chemotherapy alone. In Study 7 (metastatic gastric cancer) on thetrastuzumab containing arm as compared to the chemotherapy alone arm, the incidence of NCI-CTC Grade
3/4 neutropenia was 36.8% compared to 28.9%; febrile neutropenia 5.1% compared to 2.8%.Infection
The overall incidences of infection (46% vs. 30% [Study 5]), of selected NCI-CTC Grade 2–5infection/febrile neutropenia (24.3% vs. 13.4% [Study 1]) and of selected Grade 3–5 infection/febrileneutropenia (2.9% vs. 1.4%) [Study 2]) were higher in patients receiving trastuzumab and chemotherapycompared with those receiving chemotherapy alone. The most common site of infections in the adjuvantsetting involved the upper respiratory tract, skin, and urinary tract.
In Study 4, the overall incidence of infection was higher with the addition of trastuzumab to AC-T but notto TCH [44% (AC-TH), 37% (TCH), 38% (AC-T)]. The incidences of NCI-CTC Grade 3-4 infection
were similar [25% (AC-TH), 21% (TCH), 23% (AC-T)] across the three arms.
In a randomized, controlled trial in treatment of metastatic breast cancer, the reported incidence offebrile neutropenia was higher (23% vs. 17%) in patients receiving trastuzumab in combination withmyelosuppressive chemotherapy as compared to chemotherapy alone.
Pulmonary Toxicity
Adjuvant Breast Cancer
Among women receiving adjuvant therapy for breast cancer, the incidence of selected NCI-CTC Grade 2-5pulmonary toxicity (14.3% vs. 5.4% [Study 1]) and of selected NCI-CTC Grade 3–5 pulmonary toxicity andspontaneous reported Grade 2 dyspnea (3.4% vs. 0.9% [Study 2]) was higher in patients receivingtrastuzumab and chemotherapy compared wit |
