Neutropenia

In randomized controlled clinical trials in the adjuvant setting, the incidence of selected NCI‑CTC Grade 4–5 neutropenia (2% vs. 0.7% [Study 2]) and of selected Grade 2–5 neutropenia (7.1% vs. 4.5% [Study 1]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. In a randomized, controlled trial in patients with metastatic breast cancer, the incidences of NCI‑CTC Grade 3/4 neutropenia (32% vs. 22%) and of febrile neutropenia (23% vs. 17%) were also increased in patients randomized to Herceptin in combination with myelosuppressive chemotherapy as compared to chemotherapy alone. In Study 7 (metastatic gastric cancer) on the Herceptin 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 2–5 infection/febrile neutropenia (22% vs. 14% [Study 1]) and of selected Grade 3–5 infection/febrile neutropenia (3.3% vs. 1.4%) [Study 2]), were higher in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone. The most common site of infections in the adjuvant setting involved the upper respiratory tract, skin, and urinary tract.

In Study4, the overall incidence of infection was higher with the addition of Herceptin to AC‑T but not to 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 of febrile neutropenia was higher (23% vs. 17%) in patients receiving Herceptin in combination with myelosuppressive 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 2–5 pulmonary toxicity (14% vs. 5% [Study 1]) and of selected NCI‑CTC Grade 3–5 pulmonary toxicity and spontaneous reported Grade2 dyspnea (3.4% vs. 1% [Study 2]) was higher in patients receiving Herceptin and chemotherapy compared with chemotherapy alone. The most common pulmonary toxicity was dyspnea (NCI‑CTC Grade 2–5: 12% vs. 4% [Study 1]; NCI‑CTC Grade 2–5: 2.5% vs. 0.1% [Study 2]).

Pneumonitis/pulmonary infiltrates occurred in 0.7% of patients receiving Herceptin compared with 0.3% of those receiving chemotherapy alone. Fatal respiratory failure occurred in 3patients receiving Herceptin, one as a component of multi‑organ system failure, as compared to 1patient receiving chemotherapy alone.

In Study3, there were 4cases of interstitial pneumonitis in Herceptin‑treated patients compared to none in the control arm.

Metastatic Breast Cancer

Among women receiving Herceptin for treatment of metastatic breast cancer, the incidence of pulmonary toxicity was also increased. Pulmonary adverse events have been reported in the post‑marketing experience as part of the symptom complex of infusion reactions. Pul