s [Study 2]) were increased in patients receiving trastuzumab and chemotherapy compared with thosereceiving chemotherapy alone. Following the administration of trastuzumab as a single agent (Study 6), theincidence of NCI-CTC Grade 3 anemia was < 1%. In Study 7 (metastatic gastric cancer), on the trastuzumab containing arm as compared to the chemotherapy alone arm, the overall incidence of anemia was 28% comparedto 21% and of NCI-CTC Grade 3/4 anemia was 12.2% compared to 10.3%.
Neutropenia
In randomized controlled clinical trials in the adjuvant setting, the incidence of selected NCI-CTC Grade 4 to 5neutropenia (1.7% vs. 0.8% [Study 2]) and of selected Grade 2 to 5 neutropenia (6.4% vs. 4.3% [Study 1]) wereincreased in patients receiving trastuzumab and chemotherapy compared with those receiving chemotherapyalone. In a randomized, controlled trial in patients with metastatic breast cancer, the incidences of NCI-CTCGrade 3/4 neutropenia (32% vs. 22%) and of febrile neutropenia (23% vs. 17%) were also increased in patientsrandomized to trastuzumab in combination with myelosuppressive chemotherapy as compared to chemotherapyalone. In Study 7 (metastatic gastric cancer) on the trastuzumab containing arm as compared to thechemotherapy 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 to 5 infection/febrileneutropenia (24.3% vs. 13.4% [Study 1]) and of selected Grade 3 to 5 infection/febrile neutropenia (2.9% vs.
1.4%) [Study 2]) were higher in patients receiving trastuzumab and chemotherapy compared with thosereceiving chemotherapy alone. The most common site of infections in the adjuvant setting 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 not toTCH [44% (AC-TH), 37% (TCH), 38% (AC-T)]. The incidences of NCI-CTC Grade 3 to 4 infection weresimilar [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 of febrileneutropenia was higher (23% vs. 17%) in patients receiving trastuzumab in combination with myelosuppressivechemotherapy 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 to 5pulmonary toxicity (14.3% vs. 5.4% [Study 1]) and of selected NCI-CTC Grade 3 to 5 pulmonary toxicity andspontaneous reported Grade 2 dyspnea (3.4% vs. 0.9% [Study 2]) was higher in patients receiving trastuzumaband chemotherapy compared with chemotherapy alone. The most common pulmonary toxicity was dyspnea(NCI-CTC Grade 2 to 5: 11.8% vs. 4.6% [Study 1]; NCI-CTC Grade 2 to 5: 2.4% vs. 0.2% [Study 2]).
Pneumonitis/pulmonary infiltrates occurred in 0.7% of patients receiving trastuzumab compared with 0.3% ofthose receiving chemotherapy alone. Fatal respiratory failure occurred in 3 patients receiving trastuzumab, oneas a component of multi-organ system failure, as compared to 1 patient receiving chemotherapy alone.
In Study 3, there were 4 cases of interstitial pneumonitis in the one-year trastuzumab treatment arm compared tonone in the observation arm at a median follow-up duration of 12.6 months.
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