Efficacy and Safety of Sunitinib in Patients with Well-Differentiated Pancreatic Neuroendocrine Tumours.
Raymond E, Kulke MH, Qin S, Yu X, Schenker M, Cubillo A, Lou W, Tomasek J, Thiis-Evensen E, Xu JM, Croitoru AE, Khasraw M, Sedlackova E, Borbath I, Ruff P, Oberstein PE, Ito T, Jia L, Hammel P, Shen L, Shrikhande SV, Shen Y, Sufliarsky J, Khan GN, Morizane C, Galdy S, Khosravan R, Fernandez KC, Rosbrook B, and Fazio N. Efficacy and safety of sunitinib in patients with well-differentiated pancreatic neuroendocrine tumours. Neuroendocrinology 2018; 107(3):237-245.
BACKGROUND: In a phase III study, sunitinib led to a significant increase in progression-free survival (PFS) versus placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data.
METHODS: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to those of the phase III study. The primary endpoint was investigator-assessed PFS per Response Evaluation Criteria in Solid Tumours v1.0 (RECIST). Other endpoints included PFS per Choi criteria, overall survival (OS), objective response rate (ORR), and adverse events (AEs).
RESULTS: Sixty-one treatment-naive and 45 previously treated patients received sunitinib. By March 19, 2016, 82 (77%) patients had discontinued treatment, mainly due to disease progression. Median treatment duration was 11.7 months. Investigator-assessed median PFS per RECIST (95% confidence interval [CI]) was 13.2 months (10.9-16.7): 13.2 (7.4-16.8) and 13.0 (9.2-20.4) in treatment-naive and previously treated patients, respectively. ORR (95% CI) per RECIST was 24.5% (16.7-33.8) in the total population: 21.3% (11.9-33.7) in treatment-naive and 28.9% (16.4-44.3) in previously treated patients. Median OS, although not yet mature, was 37.8 months (95% CI, 33.0-not estimable). The most common treatment-related AEs were neutropenia (53.8%), diarrhoea (46.2%), and leukopenia (43.4%).
CONCLUSIONS: This phase IV trial confirms sunitinib as an efficacious and safe treatment option in patients with advanced/metastatic, well-differentiated, unresectable panNETs, and supports the phase III study outcomes. AEs were consistent with the known safety profile of sunitinib.
Medical Subject Headings
Adult; Aged; Antineoplastic Agents; Disease-Free Survival; Female; Humans; Male; Middle Aged; Neuroendocrine Tumors; Pancreatic Neoplasms; Sunitinib; Survival Rate