through 5.
Chemotherapy was administered for six 21-day cycles. Median duration of trastuzumab treatment was 21weeks; median number of trastuzumab infusions administered was eight.
Table 5
Study 7: Per Patient Incidence of Adverse Reactions of All Grades (Incidence ≥ 5% between Arms) orGrade 3 /4 (Incidence > 1% between Arms) and Higher Incidence in Trastuzumab Arm
Trastuzumab FC
(N = 294)
N (%)
FC
(N = 290)
N (%)
Body System/Adverse Event All Grades Grades 3/4 All Grades Grades 3/4
Investigations
230 (78) 101 (34) 212 (73) 83 (29) Neutropenia
Hypokalemia 83 (28) 28 (10) 69 (24) 16 (6)
Anemia 81 (28) 36 (12) 61 (21) 30 (10)
Thrombocytopenia 47 (16) 14 (5) 33 (11) 8 (3)
Blood and Lymphatic System Disorders
Febrile Neutropenia 15 (5) 8 (3)
Gastrointestinal Disorders
Diarrhea 109 (37) 27 (9) 80 (28) 11 (4)
Stomatitis 72 (24) 2 (1) 43 (15) 6 (2)
Dysphagia 19 (6) 7 (2) 10 (3) 1 (≤ 1)
Body as a Whole
Fatigue 102 (35) 12 (4) 82 (28) 7 (2)
Fever 54 (18) 3 (1) 36 (12) 0 (0)
Mucosal Inflammation 37 (13) 6 (2) 18 (6) 2 (1)
Chills 23 (8) 1 (≤1) 0 (0) 0 (0)
Metabolism and Nutrition Disorders
Weight Decrease 69 (23) 6 (2) 40 (14) 7 (2)
Infections and Infestations
Upper Respiratory Tract Infections 56 (19) 0 (0) 29 (10) 0 (0)
Nasopharyngitis 37 (13) 0 (0) 17 (6) 0 (0)
Renal and Urinary Disorders
Renal Failure and Impairment 53 (18) 8 (3) 42 (15) 5 (2)
Nervous System Disorders
Dysgeusia 28 (10) 0 (0) 14 (5) 0 (0)
The following subsections provide additional detail regarding adverse reactions observed in clinical trials ofadjuvant breast cancer, metastatic breast cancer, metastatic gastric cancer, or post-marketing experience.
Cardiomyopathy
Serial measurement of cardiac function (LVEF) was obtained in clinical trials in the adjuvant treatment ofbreast cancer. In Study 3, the median duration of follow-up was12.6 months (12.4 months in theobservation arm; 12.6 months in the 1-year trastuzumab arm); and in Studies 1 and 2, 7.9 years in the AC-Tarm, 8.3 years in the AC-TH arm. In Studies 1 and 2, 6% of all randomized patients with post-AC LVEFeva luation were not permitted to initiate trastuzumab following completion of AC chemotherapy due tocardiac dysfunction (LVEF < LLN or ≥ 16 point decline in LVEF from baseline to end of AC).
Following initiation of trastuzumab therapy, the incidence of new-onset dose-limiting myocardialdysfunction was higher among patients receiving trastuzumab and paclitaxel as compared to thosereceiving paclitaxel alone in Studies 1 and 2, and in patients receiving one-year trastuzumabmonotherapy compared to observation in Study 3 (see Table 6, Figures 1 and 2). The per-patientincidence of new-onset cardiac dysfunction, as measured by LVEF, remained similar when compared to
the analysis performed at a median follow-up of 2.0 years in the AC-TH arm. This analysis also showedevidence of reversibility of left ventricular dysfunction, with 64.5% of patients who experiencedsymptomatic CHF in the AC-TH group being asymptomatic at latest follow-up, and 90.3% having full orpartial LVEF recovery.
Table 6a
Per-patient Incidence of New Onset Myocardial Dysfunction (by LVEF) Studies 1, 2, 3 and 4
LVEF < 50%
and Absolute Decrease from Baseline Absolute LVEF Decrease |
