ONS Connect - October 2008 - (Page 32)

Table 3 MedDRA (v. 7.1) 1 Year Herceptin Adverse Event Preferred Term (n= 1678) Cardiac Hypertension 64 (4%) Dizziness 60 (4%) Ejection Fraction Decreased 58 (3.5%) Palpitations 48 (3%) Cardiac Arrhythmiasb 40 (3%) Cardiac Failure Congestive 30 (2%) Cardiac Failure 9 (0.5%) Cardiac Disorder 5 (0.3%) Ventricular Dysfunction 4 (0.2%) Respiratory Thoracic Mediastinal Disorders Nasopharyngitis 135 (8%) Cough 81 (5%) Influenza 70 (4%) Dyspnea 57 (3%) URI 46 (3%) Rhinitis 36 (2%) Pharyngolaryngeal Pain 32 (2%) Sinusitis 26 (2%) Epistaxis 25 (2%) Pulmonary Hypertension 4 (0.2%) Interstitial Pneumonitis 4 (0.2%) Gastrointestinal Disorders Diarrhea 123 (7%) Nausea 108 (6%) Vomiting 58 (3.5%) Constipation 33 (2%) Dyspepsia 30 (2%) Upper Abdominal Pain 29 (2%) Musculoskeletal & Connective Tissue Disorders Arthralgia 137 (8%) 91 (5%) Back Pain Myalgia 63 (4%) Bone Pain 49 (3%) Muscle Spasm 46 (3%) Nervous System Disorders Headache 162 (10%) Paraesthesia 29 (2%) Skin & Subcutaneous Tissue Disorders Rash 70 (4%) Nail Disorders 43 (2%) Pruritus 40 (2%) General Disorders Pyrexia 100 (6%) Edema Peripheral 79 (5%) Chills 85 (5%) Asthenia 75 (4.5%) Influenza-like Illness 40 (2%) Sudden Death 1 (0.06%) Infections Nasopharyngitis 135 (8%) UTI 39 (3%) Immune System Disorders Hypersensitivity 10 (0.6%) Autoimmune Thyroiditis 4 (0.3%) a a : Observation (n= 1708) 35 (2%) 29 (2%) 11 (0.6%) 12 (0.7%) 17 (1%) 5 (0.3%) 4 (0.2%) 0 (0%) 0 (0%) 43 (3%) 34 (2%) 9 (0.5%) 26 (2%) 20 (1%) 6 (0.4%) 8 (0.5%) 5 (0.3%) 1 (0.06%) 0 (0%) 0 (0%) 16 (1%) 19 (1%) 10 (0.6%) 17 (1%) 9 (0.5%) 15 (1%) 98 (6%) 58 (3%) 17 (1%) 26 (2%) 3 (0.2%) 49 (3%) 11 (0.6%) 10 (0.6%) 0 (0%) 10 (0.6%) 6 (0.4%) 37 (2%) 0 (0%) 30 (2%) 3 (0.2%) 0 (0%) 43 (3%) 13 (0.8%) 1 (0.06%) 0 (0%) 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 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 Study 4 reflect exposure to Herceptin as part of an adjuvant treatment regimen from 2124 patients n = 1068; TCH: n = 1056]. The overall median treatment arms. The median number of infusions was 26 in the infusions during the chemotherapy phase and every 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 the exception of a low incidence of CHF in the TCH arm. Metastatic Breast Cancer Studies The data below reflect exposure 5, of chemotherapy with (n=235) or without (n=234) trastuzumab in patients with metastatic breast cancer, with metastatic breast cancer. Data in Table 5 are based Study 5, the median age was 52 years (range: 25–77 received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly. The percentages of patients who received Herceptin treatment for 6 months and the 352 patients treated in single agent studies (213 patients from Study 6), the median age was 50 years (range 28–86 years), 100% had breast cancer, 8% in other racial/ethnic groups. Most of the patients received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly. The percentages of patients who received Herceptin treatment for 6 months and 12 months were 31% and 16%, respectively. Table 4 Occurring in 5% of Patients in Uncontrolled Studies or and 6) (Percent of Patients) Herceptin Single + Paclitaxel Herceptin ACb Agenta Paclitaxel Alone + ACb Alone n = 352 n = 91 n = 95 n = 143 n = 135 Body as a Whole Pain 47 61 62 57 42 Asthenia 42 62 57 54 55 Fever 36 49 23 56 34 Chills 32 41 4 35 11 Headache 26 36 28 44 31 Abdominal pain 22 34 22 23 18 Back pain 22 34 30 27 15 Infection 20 47 27 47 31 Flu syndrome 10 12 5 12 6 Accidental injury 6 13 3 9 4 Allergic reaction 3 8 2 4 2 Cardiovascular Tachycardia 5 12 4 10 5 Congestive heart failure 7 11 1 28 7 Digestive Nausea 33 51 9 76 77 Diarrhea 25 45 29 45 26 Vomiting 23 37 28 53 49 Nausea and 8 14 11 18 9 vomiting Anorexia 14 24 16 31 26 Heme & Lymphatic Anemia 4 14 9 36 26 Leukopenia 3 24 17 52 34 a Metabolic Peripheral edema Edema Musculoskeletal Bone pain Arthralgia Nervous Insomnia Dizziness Paresthesia Depression Peripheral neuritis Neuropathy Respiratory Cough increased Dyspnea Rhinitis Pharyngitis Sinusitis Skin Rash Herpes simplex Acne Urogenital Urinary tract infection 10 8 7 6 14 13 9 6 2 1 26 22 14 12 9 18 2 2 5 22 10 24 37 25 22 48 12 23 13 41 27 22 22 21 38 12 11 18 20 8 18 21 13 24 39 13 16 5 22 26 5 14 7 18 3 3 14 20 11 7 8 29 24 17 20 2 4 43 42 22 30 13 27 7 3 13 17 5 7 9 15 18 11 12 2 4 29 25 16 18 6 17 9 <1 7 Data for Herceptin single agent were from 4 studies, including 213 patients from Study 6. b epirubicin) and cyclophosphamide. The following subsections provide additional detail regarding adverse reactions observed in clinical trials of adjuvant breast, metastatic breast cancer, Cardiomyopathy Serial measurement of cardiac function (LVEF) was obtained in clinical trials in the adjuvant treatment of breast cancer. months (12.4 months in the observation arm; 12.6 months Studies 1 and 2, 6% of patients were not permitted to initiate to cardiac dysfunction (LVEF < 50% or 15 point decline limiting myocardial dysfunction was higher among patients receiving Herceptin and paclitaxel as compared to those receiving paclitaxel alone in Studies 1 and 2, and in patients receiving Herceptin monotherapy compared to observation in Study 3 (see Table 5, Figures 1 and 2). Table 5a Dysfunction (by LVEF) Studies 1, 2, 3 and 4 LVEF <50% and Absolute Absolute LVEF Decrease from Baseline Decrease LVEF 10% 16% <20% and <50% decrease decrease 10% 20% Studies 1 & 2b AC TH 22.8% 18.3% 11.7% 33.4% 9.2% (n=1606) (366) (294) (188) (536) (148) AC T 9.1% 5.4% 2.2% 18.3% 2.4% (n=1488) (136) (81) (33) (272) (36) Study 3 Herceptin 8.6% 7.0% 3.8% 22.4% 3.5% (n=1678) (144) (118) (64) (376) (59) Observation 2.7% 2.0% 1.2% 11.9% 1.2% (n=1708) (46) (35) (20) (204) (21) Study 4c TCH 8.5% 5.9% 3.3% 34.5% 6.3% (n=1056) (90) (62) (35) (364) (67) 17% 13.3% 9.8% 44.3% 13.2% AC TH (n=1068) (182) (142) (105) (473) (141) 9.5% 6.6% 3.3% 34% 5.5% AC T (n=1050) (100) (69) (35) (357) (58) a For Studies 1, 2 and 3, events are counted from the beginning of Herceptin treatment. For Study 4, events are counted from the date of randomization. bStudies 1 and 2 regimens: doxorubicin and cyclophosphamide followed by paclitaxel TH). cStudy 4 regimens: doxorubicin and cyclophosphamide followed by TH); docetaxel and carboplatin plus Herceptin (TCH). The incidence of Grade 3/4 adverse reactions was <1% in both arms for each listed term. bHigher level grouping term. The data from Studies 1 and 2 were obtained from 3206 patients enrolled, of which 1635 patients received Herceptin; the median treatment duration was 50 weeks. Grade 2–5 dyspnea were collected during and for up to 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

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ONS Connect - October 2008

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