6.4 Cardiovascular Events
See 5 WARNINGS AND PRECAUTIONS for information on left ventricular dysfunction and QTc interval prolongation.

Two patients with cytokine-refractory MRCC experienced Grade 3 myocardial ischemia, one had Grade 2 "cardiovascular toxicity" reported as an adverse event and one patient experienced a fatal myocardial infarction while on treatment.

6.5 Venous Thromboembolic Events
Seven patients (3%) on SUTENT and none on placebo in GIST Study A experienced venous thromboembolic events; five of the seven were Grade 3 deep venous thrombosis (DVT), and two were Grade 1 or 2. Four of these seven GIST patients discontinued treatment following first observation of DVT. Seven (2%) patients receiving SUTENT for treatment-naïve MRCC and four patients (2%) on the two cytokine-refractory MRCC studies had venous thromboembolic events reported. Six of these patients had pulmonary embolism, one was Grade 3 and five were Grade 4, and five patients had DVT, one each with Grade 1 and 4, and three with Grade 3. Dose interruption occurred in one of these cases. In treatment-naïve MRCC patients receiving IFN-α, six (2%) venous thromboembolic events occurred; one patient (<1%) experienced a Grade 3 DVT and five patients (1%) had pulmonary embolism, one Grade 1 and four with Grade 4.

6.6 Seizures
In clinical studies of SUTENT, seizures have been observed in subjects with radiological evidence of brain metastases. In addition, there have been rare (<1%) reports of subjects presenting with seizures and radiological evidence of reversible posterior leukoencephalopathy syndrome (RPLS). None of these subjects had a fatal outcome to the event. Patients with seizures and signs/symptoms consistent with RPLS, such as hypertension, headache, decreased alertness, altered mental functioning, and visual loss, including cortical blindness should be controlled with medical management including control of hypertension. Temporary suspension of SUTENT is recommended; following resolution, treatment may be resumed at the discretion of the treating physician.

6.7 Laboratory Abnormalities/Testing

Hematologic Events

Grade 3 and 4 neutropenia were reported in 19 (9%) and 3 (2%) patients with GIST on SUTENT. Grade 4 neutropenia was reported in 3 (1%) and 1 (1%) patients receiving SUTENT for treatment-naïve and cytokine-refractory MRCC, respectively. Grade 3 neutropenia was reported in 41 (11%) and 21 (12%) patients receiving SUTENT for treatment-naïve and cytokine-refractory MRCC, respectively. Twenty-four (7%) and 0 patients treated with IFN-α for treatment-naïve MRCC had Grade 3 and 4 neutropenia, respectively. In Study A, one GIST patient each in the SUTENT and placebo groups had febrile neutropenia. Grade 3 and 4 thrombocytopenia was reported in 7 (4%) and 1 (1%) patients with GIST on SUTENT and 35 (11%) and 0 patients with MRCC, respectively. No GIST patients receiving placebo experienced either Grade 3 or 4 neutropenia or thrombocytopenia. The rates of dose reductions and delays for hematologic abnormalities were 2% and 4% for neutropenia, 0% and 2% for anemia, and 1% and 1% for thrombocytopenia for GIST and cytokine-refractory MRCC patients, respectively. One cytokine-refractory MRCC patient with an adverse event report of Grade 4 thrombocytopenia discontinued treatment.

Patients receiving SUTENT sh