patients (21%) on IFN-α. Dose interruptions occurred in 142 patients (38%) on SUTENT and 115 patients (32%) on IFN-α. The rates of treatment-emergent, non-fatal adverse events resulting in permanent discontinuation were 8% and 13% in the SUTENT and IFN-α groups, respectively. Most treatment-emergent adverse events in both study arms were Grade 1 or 2 in severity. Grade 3 or 4 treatment-emergent adverse events were reported in 63% versus 48% of patients on SUTENT versus IFN-α, respectively. Diarrhea, mucositis/ stomatitis, dyspepsia, hypertension, bleeding, skin abnormalities, and altered taste were more common in patients receiving SUTENT. Table 3 compares the incidence of common (≥10%) treatment-emergent adverse events for patients receiving SUTENT versus IFN-α.
Data on SUTENT treatment in 169 patients with cytokine-refractory MRCC enrolled in Studies 1 and 2 are also included in Table 3. Dose interruptions occurred in 48 patients (45%) on Study 1 and 45 patients (71%) on Study 2; one or more dose reductions occurred in 23 patients (22%) on Study 1 and 22 patients (35%) on Study 2.
Other significant adverse events occurring in cytokine-refractory MRCC patients receiving SUTENT included peripheral neuropathy (10%), appetite disturbance (9%), blistering of the skin (7%), periorbital edema (7%) and increased lacrimation (6%).
In the treatment-naive MRCC study, 20 (17%) versus 14 patients (10%) experienced treatment-emergent Grade 4 chemistry laboratory abnormalities on SUTENT versus IFN-α, respectively. The most common Grade 4 chemistry abnormalities were hyperuricemia (12% on SUTENT, 8% on IFN-α) and increased lipase (3% on SUTENT, 1% on IFN-α). The most common Grade 3 chemistry abnormalities observed on both arms were increased lipase (13% on SUTENT, 5% on IFN-α) and hypophosphatemia (4% on SUTENT, 6% on IFN-α). Other common Grade 3 laboratory abnormalities on SUTENT were hyponatremia (5%) and increased amylase (4%), and on IFN-α was hyperglycemia (6%).
Common treatment-emergent Grade 3 and 4 chemistry laboratory abnormalities in patients on SUTENT in the cytokine-refractory MRCC studies included increased lipase (16%), increased amylase (5%), hypophosphatemia (10%), and hyperuricemia (10%).
Table 3. Treatment-Emergent Adverse Events Reported in at Least 10% of Patients with MRCC Who Received SUTENT or IFN-α * Treatment-Naïve MRCC Cytokine-Refractory MRCC
SUTENT
(n=375) IFN-α
(n=360) SUTENT
(N=169)
Adverse Event, n (%) All Grades Grade 3/4† All Grades Grade 3/4‡ All Grades Grade 3/4§
*
Common Toxicity Criteria for Adverse Events (CTCAE), Version 3.0
†
Grade 4 AEs in patients on SUTENT included arthralgia (<1%), asthenia (<1%), back pain (1%), dehydration (<1%), fatigue (<1%), limb pain (<1%) and rash (<1%).
‡
Grade 4 AEs in patients on IFN-α included dyspnea (1%), depression (<1%) and fatigue (1%).
§
There were no Grade 4 adverse events among the events reported with a ≥10% incidence in the cytokine-refractory MRCC population.
¶
Includes flank pain
#
Includes ageusia, hypogeusia and dysgeusia
Þ
Includes decreased appetite
ß
Includes one patient with non-treatment-related Grade 5 gastric hemorrhage
Any 370 (99)
