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In May 2011, the FDA approved sunitinib (Sutent) for the treatment of progressive well-differentiated pancreatic neuroendocrine tumors (pNET) in patients with unresectable, locally advanced, or metastatic disease. In the pivotal study that led to the approval dose was reduced to 37.5-mg because of toxicities that were seen with the 50-mg dose in earlier trials, notes Diane Reidy-Lagunes, MD, MS.
Data from the study showed that the sunitinib arm demonstrated a median progression free survival (PFS) of 11.4 months compared with 5.5 months in the placebo arm. Hypertension commonly occurs with sunitinib at the 37.5 mg dose, Reidy-Lagunes notes. However, this side effect is typically something that can be controlled with 1 or 2 antihypertensive medications. Additionally, treatment with sunitinib is typically associated with hand-foot syndrome, diarrhea, and sometimes a lowering of the blood counts.
Positive data for sunitinib and everolimus as treatments for patients with pNETs were published in the New England Journal of Medicine
around the same time, with both agents gaining FDA approvals for pNETs in 2011. This marked an exciting time for this disease state, Reidy-Lagunes believes, since there were two new agents both tested in rigorous, well-designed clinical trials.
As a result of these similar findings and timeframes, choosing between everolimus and sunitinib for patients with pNETs is very difficult, suggests Jonathan R. Strosberg, MD. The Kaplan-Meier curves for PFS for the two treatments are virtually superimposable. The side effect profiles are different, but specialists are split evenly down the middle as to whether they think sunitinib or everolimus is more tolerable.
As a result of the similarities between the drugs, the treatment selection can be based on patient comorbidities, Strosberg notes. If a patient has underlying diabetes, sunitinib is the ideal therapy. If a patient has underlying significant hypertension, everolimus might be a better choice. Additionally, the continuous schedule with everolimus may be more tolerable than the 4-week on, 2-week off schedule for sunitinib.
In about 30% of patients, Strosberg has to reduce the sunitinib dose to 25 mg as a result of side effects. With everolimus, the 10-mg continuous dosing needs to be reduced in about 40% of patients. Some patients treated with everolimus experience mouth pain while others, especially elderly patients, may experience a slow progression of side effects, such as fatigue, weight loss, or malaise. If this occurs, Strosberg recommends reducing the dose to 5 mg.