The most common adverse reactions (≥20%) in patients with GIST, RCC or pNET are fatigue, asthenia, fever, diarrhea, nausea, mucositis/stomatitis, vomiting, dyspepsia, abdominal pain, constipation, hypertension, peripheral edema, rash, hand-foot syndrome, skin discoloration, dry skin, hair color changes, altered taste, headache, back pain, arthralgia, extremity pain, cough, dyspnea, anorexia, and bleeding. The potentially serious adverse reactions of hepatotoxicity, left ventricular dysfunction, QT interval prolongation, hemorrhage, hypertension, thyroid dysfunction, and adrenal function are discussed in Warnings and Precautions (5). Other adverse reactions occurring in GIST, RCC and pNET studies are described below.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
6.1Adverse Reactions in GIST Study A
Median duration of blinded study treatment was two cycles for patients on SUTENT (mean 3.0, range 1–9) and one cycle (mean 1.8, range 1–6) for patients on placebo at the time of the interim analysis. Dose reductions occurred in 23 patients (11%) on SUTENT and none on placebo. Dose interruptions occurred in 59 patients (29%) on SUTENT and 31 patients (30%) on placebo. The rates of treatment-emergent, non-fatal adverse reactions resulting in permanent discontinuation were 7% and 6% in the SUTENT and placebo groups, respectively.
Most treatment-emergent adverse reactions in both study arms were Grade 1 or 2 in severity. Grade 3 or 4 treatment-emergent adverse reactions were reported in 56% versus 51% of patients on SUTENT versus placebo, respectively, in the double-blind treatment phase of the trial. Table 1 compares the incidence of common (≥10%) treatment-emergent adverse reactions for patients receiving SUTENT and reported more commonly in patients receiving SUTENT than in patients receiving placebo.
Table 1. Adverse Reactions Reported in Study A in at Least 10% of GIST Patients who Received SUTENT in the Double-Blind Treatment Phase and More Commonly Than in Patients Given Placebo* Adverse Reaction,
n (%) GIST
SUTENT (n=202) Placebo (n=102)
All Grades Grade 3/4 All Grades Grade 3/4
Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0
Includes decreased appetite
Any 114 (56) 52 (51)
Gastrointestinal
Diarrhea 81 (40) 9 (4) 27 (27) 0 (0)
Mucositis/stomatitis 58 (29) 2 (1) 18 (18) 2 (2)
Constipation 41 (20) 0 (0) 14 (14) 2 (2)
Cardiac
Hypertension 31 (15) 9 (4) 11 (11) 0 (0)
Dermatology
Skin discoloration 61 (30) 0 (0) 23 (23) 0 (0)
Rash 28 (14) 2 (1) 9 (9) 0 (0)
Hand-foot syndrome 28 (14) 9 (4) 10 (10) 3 (3)
Neurology
Altered taste 42 (21) 0 (0) 12 (12) 0 (0)
Musculoskeletal
Myalgia/limb pain 28 (14) 1 (1) 9 (9) 1 (1)
Metabolism/Nutrition
Anorexia† 67 (33) 1 (1) 30 (29) 5 (5)
Asthenia 45 (22) 10 (5) 11 (11) 3 (3)
In the double-blind treatment phase of GIST Study A, oral pain other than mucositis/stomatitis occurred in 12 patients (6%) on SUTENT versus 3 (3%) on placebo. Hair color changes occurred in 15 patients (7%) on SUTENT versus 4 (4%) on placebo. Alopecia wa |
