s observed in 10 patients (5%) on SUTENT versus 2 (2%) on placebo.
Table 2 provides common (≥10%) treatment-emergent laboratory abnormalities.
Table 2. Laboratory Abnormalities Reported in Study A in at Least 10% of GIST Patients Who Received SUTENT or Placebo in the Double-Blind Treatment Phase* Laboratory Parameter, n (%) GIST
SUTENT (n=202) Placebo (n=102)
All Grades* Grade 3/4*† All Grades* Grade 3/4*
LVEF=Left ventricular ejection fraction
Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0
Grade 4 laboratory abnormalities in patients on SUTENT included alkaline phosphatase (1%), lipase (2%), creatinine (1%), potassium decreased (1%), neutrophils (2%), hemoglobin (2%), and platelets (1%).
Grade 4 laboratory abnormalities in patients on placebo included amylase (1%), lipase (1%), and hemoglobin (2%).
Any 68 (34) 22 (22)
Gastrointestinal
AST / ALT 78 (39) 3 (2) 23 (23) 1 (1)
Lipase 50 (25) 20 (10) 17 (17) 7 (7)
Alkaline phosphatase 48 (24) 7 (4) 21 (21) 4 (4)
Amylase 35 (17) 10 (5) 12 (12) 3 (3)
Total bilirubin 32 (16) 2 (1) 8 (8) 0 (0)
Indirect bilirubin 20 (10) 0 (0) 4 (4) 0 (0)
Cardiac
Decreased LVEF 22 (11) 2 (1) 3 (3) 0 (0)
Renal/Metabolic
Creatinine 25 (12) 1 (1) 7 (7) 0 (0)
Potassium decreased 24 (12) 1 (1) 4 (4) 0 (0)
Sodium increased 20 (10) 0 (0) 4 (4) 1 (1)
Hematology
Neutrophils 107 (53) 20 (10) 4 (4) 0 (0)
Lymphocytes 76 (38) 0 (0) 16 (16) 0 (0)
Platelets 76 (38) 10 (5) 4 (4) 0 (0)
Hemoglobin 52 (26) 6 (3) 22 (22) 2 (2)
After an interim analysis, the study was unblinded, and patients on the placebo arm were given the opportunity to receive open-label SUTENT treatment [see Clinical Studies (14.1)]. For 241 patients randomized to the SUTENT arm, including 139 who received SUTENT in both the double-blind and open-label treatment phases, the median duration of SUTENT treatment was 6 cycles (mean 8.5, range 1 – 44). For the 255 patients who ultimately received open-label SUTENT treatment, median duration of study treatment was 6 cycles (mean 7.8, range 1 – 37) from the time of the unblinding. A total of 118 patients (46%) required dosing interruptions, and a total of 72 patients (28%) required dose reductions. The incidence of treatment-emergent adverse reactions resulting in permanent discontinuation was 20%. The most common Grade 3 or 4 treatment-related adverse reactions experienced by patients receiving SUTENT in the open-label treatment phase were fatigue (10%), hypertension (8%), asthenia (5%), diarrhea (5%), hand-foot syndrome (5%), nausea (4%), abdominal pain (3%), anorexia (3%), mucositis (2%), vomiting (2%), and hypothyroidism (2%).
6.2Adverse Reactions in the Treatment-Naïve RCC Study
The as-treated patient population for the treatment-naive RCC study included 735 patients, 375 randomized to SUTENT and 360 randomized to IFN-α. The median duration of treatment was 11.1 months (range: 0.4 – 46.1) for SUTENT treatment and 4.1 months (range: 0.1 – 45.6) for IFN-α treatment. Dose interruptions occurred in 202 patients (54%) on SUTENT and 141 patients (39%) on IFN-α. Dose reductions occurred in 194 patients (52%) on SUTENT and 98 patients (27%) on IFN-α. Discontinuation rates due to adverse reactions were 20% for SUTENT and 24% for IFN-α. Most treatment-emergent adverse rea |
