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ORLANDO -- Patients with progressive pancreatic neuroendocrine tumors lived twice as long without progression when treated with sunitinib (Sutent) compared with placebo, data from a French clinical trial showed.

Median overall survival had not been reached in the sunitinib arm, but sunitinib treatment was associated with a 60% reduction in hazard ratio compared with placebo. More than 90% of patients in the sunitinib group remained alive at six months, Eric Raymond, MD, reported here at the Gastrointestinal Cancers Symposium.

"Sunitinib continuous daily dosing resulted in clinically significant improvement in the median progression-free survival (PFS), improvement in overall survival, and a clinically significant increase in overall response rate versus placebo," said Raymond, of Hopital Beaujon in Clichy, France.

Most of the survival benefit owed to disease stabilization, as fewer than 10% of patients had objective responses.

The finding suggests that sunitinib might facilitate use of second- and third-line therapies that could build on the delayed progression and extended survival, he added.

Moreover, these findings appear to confirm results of phase I-II studies that showed sunitinib activity in pancreatic neuroendocrine tumors. In an open-label phase II study, for example, treatment with sunitinib led to partial responses in 16.7% of patients and stable disease ≥6 months in 56.1%, and median time to progression of 7.7 months in 66 patients, Raymond said.

Those favorable early benefits led to this multicenter phase III trial involving 170 patients, who received sunitinib 37.5 mg/d or placebo. Treatment continued until progression, death, withdrawal, and development of unacceptable toxicity. All patients also received best supportive care.

The primary endpoint was progression-free survival. Secondary endpoints included overall survival, overall response rate, time to response, duration of response, safety, and patient-reported outcomes.

The patients' median age was 56, and 48% were men. All but one patient had ECOG 0-1 performance status. About half of the tumors were nonfunctioning. Among functioning tumors, gastrinomas accounted for 11%, other/multiple neuropeptide for about 8%, and unspecified for 22%.

The median progression-free survival was 11.4 months in the sunitinib group and 5.5 months with placebo (HR 0.418, P=0.0001). Patients treated with sunitinib had a 71.3% probability of being alive and free of disease at six months compared with 43.2% of the placebo group.

Overall survival had not been reached after a median follow-up of 10 to 11 months. The probability of being alive at six months was 92.6% in the sunitinib arm and 85.2% in the placebo group. Kaplan-Meier analysis revealed a significant advantage in favor of the sunitinib arm (HR 0.409, P=0.0204).

Sunitinib was associated with an overall response rate of 9.3%, consisting of two complete responses and six partial responses. Additionally, 62.8% of patients in the sunitinib group had stable disease. The median response duration was 8.1 months. No objective responses occurred in the placebo group, but 60% had stable disease.

Adverse events occurred more often in the sunitinib group, but grade 3+ events were uncommon in both groups.

Although no unexpected adverse events were observed, Raymond said patients should be advised of the potential for graying of the hair, which occurred in almost 30% of sunitinib-treated patients.

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