Efficacy and safety of sunitinib in Japanese patients with progressive, advanced/metastatic, well-differentiated, unresectable pancreatic neuroendocrine tumors: final analyses from a Phase II study

BACKGROUND: In an interim analysis of a Phase II trial in Japanese patients with pancreatic neuroendocrine tumors (panNETs), sunitinib demonstrated antitumor activity with an objective response rate (ORR) of 50% (95% confidence interval [CI], 21–79) and a median progression-free survival (PFS) of 16.8 months (95% CI, 9.3–26.2). Here, we report the final analyses of efficacy and safety, as well as additional analyses, from this Phase II study. METHODS: This was a multicenter, open-label, Phase II trial (NCT01121562) of sunitinib in Japanese patients with panNETs. Patients received oral sunitinib 37.5 mg/day on a continuous daily dosing schedule. Dose modifications were permitted. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included ORR, PFS, overall survival (OS), safety and pharmacokinetics. RESULTS: Of 12 patients enrolled and treated, all discontinued treatment—the majority (n = 8) owing to disease progression. Most patients were male (n = 8), <65 years of age (n = 11) and had a non-functional tumor (n = 10). The median (range) number of days on drug was 323.5 (22–727). The CBR (95% CI) was 75.0% (42.8–94.5). ORR (95% CI) was 50.0% (21.1–78.9). Median (95% CI) PFS was 16.8 (9.3–26.2) months; however, median (95% CI) OS was not reached (22.0–not estimable). Most common adverse events (AEs; all-causality) were diarrhea (n = 10; 83.3%), hand-foot syndrome (n = 8; 66.7%) and hypertension (n = 8; 66.7%). CONCLUSIONS: These results support the efficacy and safety of sunitinib in Japanese patients with panNETs. Appropriate AE management through dose reduction and interruption may prolong sunitinib treatment and maximize its efficacy.