0.2
Abdominal pain 18.6 0.8 17.6 1.6
Vomiting 19.2 0.8 29.9 4.5
Diarrhea 24.1 1.6 79.7 20.7
Constipation 26.5 0.4 11.1 0
Nausea 39.8 0.8 45.1 2.5
General Disorders and Administration
Peripheral edema 7.1 0 8.2 0.2
Chills 7.6 0 3.1 0
Pyrexia 18.6 0.2 8.4 0.4
Asthenia 17.8 0.4 17.6 1.6
Fatigue 36.3 2.5 28.3 3.5
Hepatobiliary Disorders
Nodular regenerative hyperplasia* 0.4 ND 0 0
Portal hypertension* 0.4 0.2 0 0
Immune System Disorders
Drug hypersensitivity 2.2 0 0.8 0
Injury, Poisoning, and Procedural
Infusion-related reaction 1.4 0 0.2 0
Infections and Infestations
Urinary tract infection 9.4 0.6 3.9 0
Investigations
Blood alkaline phosphatase increased 4.7 0.4 3.7 0.4
Increased transaminases 28.8 8.0 14.3 2.5
Metabolism and Nutrition Disorders
Hypokalemia 10.2 2.7 9.4 4.7
Musculoskeletal and Connective Tissue Disorders
Myalgia 14.1 0.6 3.7 0
Arthralgia 19.2 0.6 8.4 0
Musculoskeletal pain 36.1 1.8 30.5 1.4
Nervous System Disorders
Dysgeusia 8.0 0 4.1 0.2
Dizziness 10.2 0.4 10.7 0.2
Peripheral neuropathy 21.2 2.2 13.5 0.2
Headache 28.2 0.8 14.5 0.8
Psychiatric Disorders
Insomnia 12.0 0.4 8.6 0.2
Respiratory, Thoracic, and Mediastinal Disorders
Pneumonitis 1.2 0 0 0
Dyspnea 12.0 0.8 8.0 0.4
Cough 18.2 0.2 13.1 0.2
Epistaxis 22.5 0.2 8.4 0
Skin and Subcutaneous Tissue Disorders
Pruritus 5.5 0.2 9.2 0
Rash 11.6 0 27.5 1.8
Vascular Disorders
Hypertension 5.1 1.2 2.3 0.4
Table 7 Selected Laboratory Abnormalities Parameter Kadcyla
(3.6 mg/kg) Lapatinib (1250 mg) + Capecitabine (2000 mg/m2)
All Grade % Grade 3 % Grade 4 % All Grade % Grade 3 % Grade 4 %
Increased bilirubin 17 <1 0 57 2 0
Increased AST 98 7 <1 65 3 0
Increased ALT 82 5 <1 54 3 0
Decreased platelet count 83 14 3 21 <1 <1
Decreased hemoglobin 60 4 1 64 3 <1
Decreased neutrophils 39 3 <1 38 6 2
Decreased potassium 33 3 0 31 6 <1
Immunogenicity
As with all therapeutic proteins, there is the potential for an immune response to Kadcyla. A total of 836 patients from six clinical studies were tested at multiple time points for anti-therapeutic antibody (ATA) responses to Kadcyla. Following Kadcyla dosing, 5.3% (44/836) of patients tested positive for anti-Kadcyla antibodies at one or more post-dose time points. The presence of Kadcyla in patient serum at the time of ATA sampling may interfere with the ability of this assay to detect anti-Kadcyla antibodies. As a result, data may not accurately reflect the true incidence of anti-Kadcyla antibody development. In addition, neutralizing activity of anti-Kadcyla antibodies has not been assessed.
Immunogenicity data are highly dependent on the sensitivity and specificity of the test methods used. Additionally, the observed incidence of a positive result in a test method may be influenced by several factors, including sample handling, timing of sample collection, drug interference, concomitant medication and the underlying disease. Therefore, comparison of the incidence of antibodies to Kadcyla with the incidence of antibodies to other products may be misleading. Clinical significance of anti-Kadcyla antibodies is not yet known.
Drug Interactions
No formal drug-drug interaction studies with Kadcyla have been conducted. In vitro studies indicate that DM1, the cytotoxic component of Kadcyla, is metabolized mainly by CYP3A4 and to a lesser extent by CYP3A5. Concomitant use of s
