on, nasopharyngitis, and dysgeusia. The most common adverse reactionswhich resulted in discontinuation of trastuzumab treatment in the absence of disease progression were infection,diarrhea, and febrile neutropenia.
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in theclinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may notreflect the rates observed in practice.
Adjuvant Breast Cancer Studies
The data below reflect exposure to one-year trastuzumab therapy across three randomized, open-label studies,Studies 1, 2, and 3, with (n = 3678) or without (n = 3363) trastuzumab in the adjuvant treatment of breastcancer.
The data summarized in Table 3 below, from Study 3, reflect exposure to trastuzumab in 1678 patients; themedian treatment duration was 51 weeks and median number of infusions was 18. Among the 3386 patientsenrolled in the observation and one-year trastuzumab arms of Study 3 at a median duration of follow-up of12.6 months in the trastuzumab arm, the median age was 49 years (range: 21 to 80 years), 83% of patients wereCaucasian, and 13% were Asian.
Table 3
Adverse Reactions for Study 3a
, All Gradesb
One Year Trastuzumab
Adverse Reaction (n = 1678)
Observation
(n = 1708)
Cardiac
Hypertension 64 (4%) 35 (2%)
Dizziness 60 (4%) 29 (2%)
Ejection Fraction Decreased 58 (3.5%) 11 (0.6%)
Palpitations 48 (3%) 12 (0.7%)
Cardiac Arrhythmiasc 40 (3%) 17 (1%)
Cardiac Failure Congestive 30 (2%) 5 (0.3%)
Cardiac Failure 9 (0.5%) 4 (0.2%)
Cardiac Disorder 5 (0.3%) 0 (0%)
Ventricular Dysfunction 4 (0.2%) 0 (0%)
Respiratory Thoracic Mediastinal Disorders
Cough 81 (5%) 34 (2%)
Influenza 70 (4%) 9 (0.5%)
Dyspnea 57 (3%) 26 (2%)
URI 46 (3%) 20 (1%)
Rhinitis 36 (2%) 6 (0.4%)
Pharyngolaryngeal Pain 32 (2%) 8 (0.5%)
Sinusitis 26 (2%) 5 (0.3%)
Epistaxis 25 (2%) 1 (0.06%)
Pulmonary Hypertension 4 (0.2%) 0 (0%)
Interstitial Pneumonitis 4 (0.2%) 0 (0%)
Gastrointestinal Disorders
Diarrhea 123 (7%) 16 (1%)
Nausea 108 (6%) 19 (1%)
Vomiting 58 (3.5%) 10 (0.6%)
Constipation 33 (2%) 17 (1%)
Dyspepsia 30 (2%) 9 (0.5%)
Upper Abdominal Pain 29 (2%) 15 (1%)
Musculoskeletal & Connective Tissue Disorders
Arthralgia 137 (8%) 98 (6%)
Back Pain 91 (5%) 58 (3%)
Myalgia 63 (4%) 17 (1%)
Bone Pain 49 (3%) 26 (2%)
Muscle Spasm 46 (3%) 3 (0.2%)
Nervous System Disorders
Headache 162 (10%) 49 (3%)
Paraesthesia 29 (2%) 11 (0.6%)
Skin & Subcutaneous Tissue Disorders
Rash 70 (4%) 10 (0.6%)
Nail Disorders 43 (2%) 0 (0%)
Pruritus 40 (2%) 10 (0.6%)
General Disorders
Pyrexia 100 (6%) 6 (0.4%)
Edema Peripheral 79 (5%) 37 (2%)
Chills 85 (5%) 0 (0%)
Asthenia 75 (4.5%) 30 (2%)
Influenza-like Illness 40 (2%) 3 (0.2%)
Sudden Death 1 (0.06%) 0 (0%)
Infections
Nasopharyngitis 135 (8%) 43 (3%)
UTI 39 (3%) 13 (0.8%)
Immune System Disorders
Hypersensitivity 10 (0.6%) 1 (0.06%)
Autoimmune Thyroiditis 4 (0.3%) 0 (0%) a Median follow-up duration of 12.6 months in the one-year trastuzumab treatment arm.
b The incidence of Grade 3 or higher adverse reactions was <1% in both arms for each listed term.
c Higher level grouping term.
In Study 3, a comparison of 3-weekly trastuzumab treatment for two years versus one year was also performed.
The rate of asymptomatic cardiac dysfunction was |
