The data from Studies 1 and 2 were obtained from 3206patients, of whom 1635received Herceptin; the median treatment duration was 50weeks. The median age was 49years (range: 24–80); 84%of patients were White, 7%Black, 4% Hispanic, and 4%Asian.

In Study 1, only Grade 3–5 adverse events, treatment‑related Grade 2 events, and Grade 2–5 dyspnea were collected during and for up to 3 months following protocol‑specified treatment. The following non‑cardiac adverse reactions of Grade 2–5 occurred at an incidence of at least 2% greater among patients randomized to Herceptin plus chemotherapy as compared to chemotherapy alone: arthralgia (31% vs. 28%), fatigue (28% vs. 22%), infection (22% vs. 14%), hot flashes (17% vs. 15%), anemia (13% vs. 7%), dyspnea (12% vs. 4%), rash/desquamation (11% vs. 7%), neutropenia (7% vs. 5%), headache (6% vs. 4%), and insomnia (3.7% vs. 1.5%). The majority of these events were Grade 2 in severity.

In Study 2, data collection was limited to the following investigator‑attributed treatment‑related adverse reactions NCI‑CTC Grade 4 and 5 hematologic toxicities, Grade 3–5 non‑hematologic toxicities, selected Grade 2–5 toxicities associated with taxanes (myalgia, arthralgias, nail changes, motor neuropathy, sensory neuropathy) and Grade 1–5 cardiac toxicities occurring during chemotherapy and/or Herceptin treatment. The following non‑cardiac adverse reactions of Grade 2–5 occurred at an incidence of at least 2% greater among patients randomized to Herceptin plus chemotherapy as compared to chemotherapy alone: arthralgia (11% vs. 8.4%), myalgia (10% vs. 8%), nail changes (9% vs. 7%), and dyspnea (2.5% vs. 0.1%). The majority of these events were Grade 2 in severity.

Safety data from Study4 reflect exposure to Herceptin as part of an adjuvant treatment regimen from 2124patients receiving at least one dose of study treatment [AC‑TH: n = 1068; TCH: n = 1056]. The overall median treatment duration was 54weeks in both the AC‑TH and TCH arms. The median number of infusions was 26 in the AC‑TH arm and 30 in the TCH arm, including weekly infusions during the chemotherapy phase and every three week dosing in the monotherapy period. Among these patients, the median age was 49years (range 22to 74years). In Study4, the toxicity profile was similar to that reported in Studies1, 2, and 3 with the exception of a low incidence of CHF in the TCH arm.

Metastatic Breast Cancer Studies

The data below reflect exposure to Herceptin in one randomized, open‑label study, Study 5, of chemotherapy with (n=235) or without (n=234) trastuzumab in patients with metastatic breast cancer, and one single‑arm study (Study 6; n=222) in patients with metastatic breast cancer. Data in Table 4 are based on Studies 5 and 6.

Among the 464patients treated in Study 5, the median age was 52years (range: 25–77years). Eighty‑nine percent were White, 5%Black, 1%Asian and 5%other racial/ethnic groups. All patients received 4mg/kg initial dose of Herceptin followed by 2mg/kg weekly. The percentages of patients who received Herceptin treatment for ≥ 6months and ≥ 12months were 58% and 9%, respectively.

Among the 352patients treated in single agent studies (213patients from Study 6), the median age was 50years (range 28–86years), 86% were White, 3% were Black, 3% were Asian, and 8% in other racial/e