1 years (range 18 to 61 years), 89% were Caucasian, and 34% were male. The median duration of blinded study treatment was 48 weeks (range 2 to 115 weeks) for patients receiving AFINITOR and 45 weeks (range 9 to 115 weeks) for those receiving placebo.
The most common adverse reaction reported for AFINITOR (incidence ≥ 30%) was stomatitis. The most common Grade 3-4 adverse reactions (incidence ≥ 2%) were stomatitis and amenorrhea. The most common laboratory abnormalities (incidence ≥ 50%) were hypercholesterolemia, hypertriglyceridemia, and anemia. The most common Grade 3-4 laboratory abnormality (incidence ≥ 3%) was hypophosphatemia.
The rate of adverse reactions resulting in permanent discontinuation was 3.8% in the AFINITOR-treated patients. Adverse reactions leading to permanent discontinuation in the AFINITOR arm were hypersensitivity/angioedema/bronchospasm, convulsion, and hypophosphatemia. Dose adjustments (interruptions or reductions) due to adverse reactions occurred in 52% of AFINITOR-treated patients. The most common adverse reaction leading to AFINITOR dose adjustment was stomatitis.
Table 8 compares the incidence of adverse reactions reported with an incidence of ≥ 10% for patients receiving AFINITOR and occurring more frequently with AFINITOR than with placebo. Laboratory abnormalities are described separately in Table 9.
Table 8: Adverse Reactions Reported in ≥ 10% of AFINITOR-treated Patients with Renal Angiomyolipoma Grading according to CTCAE Version 3.0
a Includes stomatitis, aphthous stomatitis, mouth ulceration, gingival pain, glossitis, and glossodynia.
AFINITOR
N=79 Placebo
N=39
All grades
% Grade 3
% Grade 4
% All grades
% Grade 3
% Grade 4
%
Any adverse reaction 100 25 5 97 8 5
Gastrointestinal disorders
Stomatitisa 78 6 0 23 0 0
Vomiting 15 0 0 5 0 0
Diarrhea 14 0 0 5 0 0
General disorders and administration site conditions
Peripheral edema 13 0 0 8 0 0
Infections and infestations
Upper respiratory tract infection 11 0 0 5 0 0
Musculoskeletal and connective tissue disorders
Arthralgia 13 0 0 5 0 0
Respiratory, thoracic and mediastinal disorders
Cough 20 0 0 13 0 0
Skin and subcutaneous tissue disorders
Acne 22 0 0 5 0 0
Amenorrhea occurred in 15% of AFINITOR-treated females (8 of 52) and 4% (1 of 26) of females in the placebo group. Other adverse reactions involving the female reproductive system were menorrhagia (10%), menstrual irregularities (10%), and vaginal hemorrhage (8%).
The following additional adverse reactions occurred in less than 10% of AFINITOR -treated patients: epistaxis (9%), decreased appetite (6%), otitis media (6%), depression (5%), abnormal taste (5%), increased blood luteinizing hormone (LH) levels (4%), increased blood follicle stimulating hormone (FSH) levels (3%), hypersensitivity (3%), ovarian cyst (3%), pneumonitis (1%), and |
