In clinical trials, Kadcyla has been eva luated as single-agent in 884 patients with HER2-positive metastatic breast cancer. The most common (frequency ≥ 25%) adverse drug reactions (ADRs) seen in 884 patients treated with Kadcyla were fatigue, nausea, musculoskeletal pain, thrombocytopenia, headache, increased transaminases, and constipation.

The ADRs described in Table 6 were identified in patients with HER2-positive metastatic breast cancer treated in a randomized trial (Study 1) [see Clinical Studies (14.1)]. Patients were randomized to receive Kadcyla or lapatinib plus capecitabine. The median duration of study treatment was 7.6 months for patients in the Kadcyla-treated group and 5.5 months and 5.3 months for patients treated with lapatinib and capecitabine, respectively. Two hundred and eleven (43.1%) patients experienced ≥ Grade 3 adverse events in the Kadcyla-treated group compared with 289 (59.2%) patients in the lapatinib plus capecitabine-treated group. Dose adjustments for Kadcyla were permitted [see Dosage and Administration (2.2)]. Thirty-two patients (6.5%) discontinued Kadcyla due to an adverse event, compared with 41 patients (8.4%) who discontinued lapatinib, and 51 patients (10.5%) who discontinued capecitabine due to an adverse event. The most common adverse events leading to Kadcyla withdrawal were thrombocytopenia and increased transaminases. Eighty patients (16.3%) treated with 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