rsus one year was alsoperformed. The rate of asymptomatic cardiac dysfunction was increased in the 2-year trastuzumab
treatment arm (8.1% versus 4.6% in the one-year trastuzumab treatment arm). More patients experiencedat least one adverse reaction of Grade 3 or higher in the 2-year trastuzumab treatment arm (20.4%)compared with the one-year trastuzumab treatment arm (16.3%).
The safety data from Studies 1 and 2 were obtained from 3655 patients, of whom 2000 receivedtrastuzumab; the median treatment duration was 51 weeks. The median age was 49 years (range: 24–80);84% of patients were White, 7% Black, 4% Hispanic, and 3% Asian.
In Study 1, only Grade 3–5 adverse events, treatment-related Grade 2 events, and Grade 2–5 dyspnea werecollected during and for up to 3 months following protocol-specified treatment. The following non-cardiacadverse reactions of Grade 2–5 occurred at an incidence of at least 2% greater among patients receivingtrastuzumab plus chemotherapy as compared to chemotherapy alone: fatigue (29.5% vs. 22.4%), infection(24.0% vs. 12.8%), hot flashes (17.1% vs. 15.0%), anemia (12.3% vs. 6.7%), dyspnea (11.8% vs. 4.6%),rash/desquamation (10.9% vs. 7.6%), leukopenia (10.5% vs. 8.4%), neutropenia (6.4% vs. 4.3%), headache(6.2% vs. 3.8%), pain (5.5% vs. 3.0%), edema (4.7% vs. 2.7%) and insomnia (4.3% vs. 1.5%). The majorityof these events were Grade 2 in severity.
In Study 2, data collection was limited to the following investigator-attributed treatment-related adversereactions: 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/ortrastuzumab treatment. The following non-cardiac adverse reactions of Grade 2–5 occurred at an incidence ofat least 2% greater among patients receiving trastuzumab plus chemotherapy as compared to chemotherapyalone: arthralgia (12.2% vs. 9.1%), nail changes (11.5% vs.6.8%), dyspnea (2.4% vs. 0.2%), and diarrhea(2.2% vs. 0%). The majority of these events were Grade 2 in severity.
Safety data from Study 4 reflect exposure to trastuzumab 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 overallmedian treatment duration was 54 weeks in both the AC-TH and TCH arms. The median number ofinfusions was 26 in the AC-TH arm and 30 in the TCH arm, including weekly infusions during thechemotherapy phase and every three week dosing in the monotherapy period. Among these patients, the
median age was 49 years (range 22 to 74 years). In Study 4, the toxicity profile was similar to that reported inStudies 1, 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 trastuzumab in one randomized, open-label study, Study 5, ofchemotherapy with (n = 235) or without (n = 234) trastuzumab in patients with metastatic breast cancer, andone single-arm study (Study 6; n = 222) in patients with metastatic breast cancer. Data in Table 4 are basedon Studies 5 and 6.
Among the 464 patients treated in Study 5, the median age was 52 years (range: 25–77 years).
Eighty- nine percent were White, 5% Black, 1% Asian and 5% other racial/ethnic groups. All patientsreceived 4 mg/kg initi |
