increased in the 2-year trastuzumab treatment arm (8.1%versus 4.6% in the one-year trastuzumab treatment arm). More patients experienced at least one adversereaction of Grade 3 or higher in the 2-year trastuzumab treatment arm (20.4%) compared with the one-yeartrastuzumab treatment arm (16.3%).
The safety data from Studies 1 and 2 were obtained from 3655 patients, of whom 2000 received trastuzumab;the median treatment duration was 51 weeks. The median age was 49 years (range: 24 to 80); 84% of patientswere White, 7% Black, 4% Hispanic, and 3% Asian.
In Study 1, only Grade 3 to 5 adverse events, treatment-related Grade 2 events, and Grade 2 to 5 dyspnea werecollected during and for up to 3 months following protocol-specified treatment.
The following non-cardiacadverse reactions of Grade 2 to 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%). Themajority of 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 to 5 non-hematologic toxicities, selectedGrade 2 to 5 toxicities associated with taxanes (myalgia, arthralgias, nail changes, motor neuropathy, and
sensory neuropathy) and Grade 1 to 5 cardiac toxicities occurring during chemotherapy and/or trastuzumabtreatment. The following non-cardiac adverse reactions of Grade 2 to 5 occurred at an incidence of at least 2%greater among patients receiving trastuzumab plus chemotherapy as compared to chemotherapy alone: 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%). Themajority of these events were Grade 2 in severity.
Safety data from Study 4 reflect exposure to trastuzumab as part of an adjuvant treatment regimen from2124 patients 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 of infusionswas 26 in the AC-TH arm and 30 in the TCH arm, including weekly infusions during the chemotherapy phaseand 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 in Studies 1, 2, and 3 with theexception 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, of chemotherapywith (n = 235) or without (n = 234) trastuzumab in patients with metastatic breast cancer, and one single-armstudy (Study 6; n = 222) in patients with metastatic breast cancer. Data in Table 4 are based on Studies 5 and 6.
Among the 464 patients treated in Study 5, the median age was 52 years (range: 25 to 77 years). Eighty-ninepercent were White, 5% Black, 1% Asian, and 5% other racial/ethnic groups. All patients received 4 mg/kginitial dose of trastuzumab followed by 2 mg/kg weekly. The percentages of patients who receivedtrastuzumabtreatment for ≥ 6 mo |
