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

• Published in: Japanese journal of clinical oncology Vol. 49; no. 4; pp. 354 - 360
• Main Authors: Ito, Tetsuhide, Tori, Masayuki, Hashigaki, Satoshi, Kimura, Nobuyuki, Sato, Kazuo, Ohki, Emiko, Sawaki, Akira, Okusaka, Takuji
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-04-2019
• Subjects: Adult; Aged; Antineoplastic Agents - therapeutic use; Disease-Free Survival; Female; Humans; Japan; Male; Middle Aged; Neuroendocrine Tumors - drug therapy; Neuroendocrine Tumors - mortality; Neuroendocrine Tumors - pathology; Original; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Progression-Free Survival; Sunitinib - therapeutic use; Japan; pancreatic neuroendocrine tumors; sunitinib; Japan; safety; efficacy
• ISSN: 1465-3621; 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyz009

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.
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.
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%).
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.