ith KADCYLA had adverse events leading to dose reductions. The most frequent adverse events leading to dose reduction of KADCYLA (in ≥ 1% of patients) included thrombocytopenia, increased transaminases, and peripheral neuropathy. Adverse events that led to dose delays occurred in 116 (23.7%) of KADCYLA treated patients. The most frequent adverse events leading to a dose delay of KADCYLA (in ≥ 1% of patients) were neutropenia, thrombocytopenia, leukopenia, fatigue, increased transaminases and pyrexia.
Table 6 reports the ADRs that occurred in patients in the KADCYLA-treated group (n=490) of the randomized trial (Study 1). Selected laboratory abnormalities are shown in Table 7. The most common ADRs seen with KADCYLA in the randomized trial (frequency > 25%) were nausea, fatigue, musculoskeletal pain, thrombocytopenia, increased transaminases, headache, and constipation. The most common NCI–CTCAE (version 3) ≥ Grade 3 ADRs (frequency >2%) were thrombocytopenia, increased transaminases, anemia, hypokalemia, peripheral neuropathy and fatigue.
Table 6 Summary of Adverse Drug Reactions Occurring in Patients on the KADCYLA Treatment Arm in the Randomized Trial (Study 1)
Adverse Drug Reactions (MedDRA)
System Organ Class
KADCYLA
(3.6 mg/kg)
n=490
Frequency rate %
Lapatinib (1250 mg) + Capecitabine (2000 mg/m2)
n=488
Frequency rate %
All grades (%)
Grade 3 – 4 (%)
All grades (%)
Grade 3 – 4 (%)
ND = Not determined
* Nodular Regenerative Hyperplasia and Portal Hypertension occurred in the same patient.
Blood and Lymphatic System Disorders
Neutropenia
6.7
2.0
9.0
4.3
Anemia
14.3
4.1
10.5
2.5
Thrombocytopenia
31.2
14.5
3.3
0.4
Cardiac Disorders
Left ventricular dysfunction
1.8
0.2
3.3
0.4
Eye Disorders
Lacrimation increased
3.3
0
2.5
0
Dry eye
3.9
0
3.1
0
Vision blurred
4.5
0
0.8
0
Conjunctivitis
3.9
0
2.3
0
Gastrointestinal Disorders
Dyspepsia
9.2
0
11.5
0.4
Stomatitis
14.1
0.2
32.6
2.5
Dry Mouth
16.7
0
4.9
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
