ccurred in 5 of 46 (11%) AFINITOR-treated females and none of the 33 females in the placebo group.
Key observed laboratory abnormalities are presented in Table 5.
Table 5: Key Laboratory Abnormalities Reported in ≥ 10% of Patients with Advanced PNET Grading according to CTCAE Version 3.0
Laboratory parameter AFINITOR
N=204 Placebo
N=203
All grades Grade 3-4 All grades Grade 3-4
% % % %
Hematology
Hemoglobin decreased 86 15 63 1
Lymphocytes decreased 45 16 22 4
Platelets decreased 45 3 11 0
WBC decreased 43 2 13 0
Neutrophils decreased 30 4 17 2
Clinical chemistry
Alkaline phosphatase increased 74 8 66 8
Glucose (fasting) increased 75 17 53 6
Cholesterol increased 66 0.5 22 0
Bicarbonate decreased 56 0 40 0
Aspartate transaminase (AST) increased 56 4 41 4
Alanine transaminase (ALT) increased 48 2 35 2
Phosphate decreased 40 10 14 3
Triglycerides increased 39 0 10 0
Calcium decreased 37 0.5 12 0
Potassium decreased 23 4 5 0
Creatinine increased 19 2 14 0
Sodium decreased 16 1 16 1
Albumin decreased 13 1 8 0
Bilirubin increased 10 1 14 2
Potassium increased 7 0 10 0.5
6.3 Clinical Study Experience in Advanced Renal Cell Carcinoma
The data described below reflect exposure to AFINITOR (n=274) and placebo (n=137) in a randomized, controlled trial in patients with metastatic renal cell carcinoma who received prior treatment with sunitinib and/or sorafenib. The median age of patients was 61 years (range 27-85), 88% were Caucasian, and 78% were male. The median duration of blinded study treatment was 141 days (range 19-451 days) for patients receiving AFINITOR and 60 days (range 21-295 days) for those receiving placebo.
The most common adverse reactions (incidence ≥ 30%) were stomatitis, infections, asthenia, fatigue, cough, and diarrhea. The most common Grade 3-4 adverse reactions (incidence ≥ 3%) were infections, dyspnea, fatigue, stomatitis, dehydration, pneumonitis, abdominal pain, and asthenia. The most common laboratory abnormalities (incidence ≥ 50%) were anemia, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, lymphopenia, and increased creatinine. The most common Grade 3-4 laboratory abnormalities (incidence ≥ 3%) were lymphopenia, hyperglycemia, anemia, hypophosphatemia, and hypercholesterolemia. Deaths due to acute respiratory failure (0.7%), infection (0.7%), and acute renal failure (0.4%) were observed on the AFINITOR arm but none on the placebo arm. The rates of treatment-emergent adverse events (irrespective of causality) resulting in permanent discontinuation were 14% and 3% for the AFINITOR and placebo treatme |
