orted in 23% of patients receiving sunitinib in a phase 3 pNET study, compared to 4% of patients receiving placebo. Severe hypertension occurred in 10% of pNET patients on sunitinib and 3% of patients on placebo. Patients should be screened for hypertension and controlled as appropriate. Temporary suspension is recommended in patients with severe hypertension that is not controlled with medical management. Treatment may be resumed once hypertension is appropriately controlled.
Haematological disorders
Decreased absolute neutrophil counts of grade 3 and 4 severity respectively were reported in 10% and 1.7% of patients on the phase 3 GIST study, in 16% and 1.6% of patients on the phase 3 MRCC study, and in 13% and 2.4% of patients on the phase 3 pNET study. Decreased platelet counts of grade 3 and 4 severity respectively were reported in 3.7% and 0.4% of patients on the phase 3 GIST study, in 8.2% and 1.1% of patients on the phase 3 MRCC study, and in 3.7% and 1.2% of patients on the phase 3 pNET study. The above events were not cumulative, were typically reversible and generally did not result in treatment discontinuation. None of these events in the phase 3 studies were fatal, but rare fatal haematological events, including haemorrhage associated with thrombocytopenia and neutropenic infections, have been reported through post-marketing experience.
Anaemia has been observed to occur early as well as late during treatment with sunitinib; Grade 3 and 4 cases have been reported.
Complete blood counts should be performed at the beginning of each treatment cycle for patients receiving treatment with sunitinib.
Cardiac disorders
Cardiovascular events, including heart failure, cardiomyopathy, and myocardial disorders, some of which were fatal, have been reported through post-marketing experience. These data suggest that sunitinib increases the risk of cardiomyopathy. No specific additional risk factors for sunitinib-induced cardiomyopathy apart from the drug-specific effect have been identified in the treated patients.
In clinical trials, decreases in LVEF of 20% and below the lower limit of normal occurred in approximately 2% of sunitinib-treated GIST patients, 4% of cytokine-refractory MRCC patients, and 2% of placebo-treated GIST patients. These LVEF declines do not appear to have been progressive and often improved as treatment continued. In the treatment-naïve MRCC study, 27% patients on sunitinib and 15% of patients on IFN-α, had an LVEF value below the lower limit of normal. Two patients (<1%) who received sunitinib were diagnosed with congestive heart failure (CHF).
In GIST patients treatment-related 'cardiac failure', 'cardiac failure congestive' or 'left ventricular failure' were reported in 0.7% of patients treated with sunitinib and 1% of patients treated with placebo. In the pivotal phase 3 GIST study (n=312), treatment-related fatal cardiac reactions occurred in 1% of patients on each arm of the study (i.e. sunitinib and placebo arms). In a phase 2 study in cytokine-refractory MRCC patients, 0.9% of patients experienced treatment-related fatal myocardial infarction and in the phase 3 study in treatment-naïve MRCC patients, 0.6% of patients on the IFN-α arm and 0% patients on the sunitinib arm experienced fatal cardiac events. In the phase 3 pNET study, one (1%) patient who received sunitinib had treatment-related fatal cardiac failure. The relationship, if any, between recepto |
