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
6.2 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.
7 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 strong CYP3A4 inhibitors (e.g., ketoconazol
