tinued treatment due to hypertension. Severe hypertension (>200 mmHg systolic or 110 mmHg diastolic) occurred in 8/202 GIST patients on SUTENT (4%), 1/102 GIST patients on placebo (1%), in 32/375 treatment-naïve RCC patients (9%) on SUTENT, in 3/360 patients (1%) on IFN-α, and in 8/80 pNET patients (10%) on SUTENT and 2/76 pNET patients (3%) on placebo.
5.6Hemorrhagic Events
Hemorrhagic events reported through post-marketing experience, some of which were fatal, have included GI, respiratory, tumor, urinary tract and brain hemorrhages. In patients receiving SUTENT in a clinical trial for treatment-naïve RCC, 140/375 patients (37%) had bleeding events compared with 35/360 patients (10%) receiving IFN-α. Bleeding events occurred in 37/202 patients (18%) receiving SUTENT in the double-blind treatment phase of GIST Study A, compared to 17/102 patients (17%) receiving placebo. Epistaxis was the most common hemorrhagic adverse event reported. Bleeding events, excluding epistaxis, occurred in 18/83 patients (22%) receiving SUTENT in the Phase 3 pNET study, compared to 8/82 patients (10%) receiving placebo. Epistaxis was reported in 17/83 patients (20%) receiving SUTENT for pNET and 4 patients (5%) receiving placebo. Less common bleeding events in GIST, RCC and pNET patients included rectal, gingival, upper gastrointestinal, genital, and wound bleeding. In the double-blind treatment phase of GIST Study A, 14/202 patients (7%) receiving SUTENT and 9/102 patients (9%) on placebo had Grade 3 or 4 bleeding events. In addition, one patient in GIST Study A taking placebo had a fatal gastrointestinal bleeding event during Cycle 2. Most events in RCC patients were Grade 1 or 2; there was one Grade 5 event of gastric bleed in a treatment-naïve patient. In the pNET study, 1/83 patients (1%) receiving SUTENT had Grade 3 epistaxis, and no patients had other Grade 3 or 4 bleeding events. In pNET patients receiving placebo, 3/82 patients (4%) had Grade 3 or 4 bleeding events.
Tumor-related hemorrhage has been observed in patients treated with SUTENT. These events may occur suddenly, and in the case of pulmonary tumors may present as severe and life-threatening hemoptysis or pulmonary hemorrhage. Fatal pulmonary hemorrhage occurred in 2 patients receiving SUTENT on a clinical trial of patients with metastatic non-small cell lung cancer (NSCLC). Both patients had squamous cell histology. SUTENT is not approved for use in patients with NSCLC. Treatment-emergent Grade 3 and 4 tumor hemorrhage occurred in 5/202 patients (3%) with GIST receiving SUTENT on Study A. Tumor hemorrhages were observed as early as Cycle 1 and as late as Cycle 6. One of these five patients received no further drug following tumor hemorrhage. None of the other four patients discontinued treatment or experienced dose delay due to tumor hemorrhage. No patients with GIST in the Study A placebo arm were observed to undergo intratumoral hemorrhage. Clinical assessment of these events should include serial complete blood counts (CBCs) and physical examinations.
Serious, sometimes fatal gastrointestinal complications including gastrointestinal perforation, have occurred rarely in patients with intra-abdominal malignancies treated with SUTENT.
5.7 Thyroid Dysfunction
Baseline laboratory measurement of thyroid function is recommended and patients with hypothyroidism or hyperthyroidism should be treated as per standard medical practice prior to the start of SUTENT treatm |
