Aim: Evaluate associations between clinical outcomes and SNPs in patients with well-differentiated pancreatic neuroendocrine tumors receiving sunitinib. Patients & methods: Kaplan-Meier and Cox proportional hazards models were used to analyze the association between SNPs and survival outcomes using data from a sunitinib Phase IV (genotyped, n = 56) study. Fisher's exact test was used to analyze objective response rate and genotype associations. Results: After multiplicity adjustment, progression-free and overall survivals were not significantly correlated with SNPs; however, a higher objective response rate was significantly associated with IL1B rs16944 G/A versus G/G (46.4 vs 4.5%; p = 0.001). Conclusion:IL1B SNPs may predict treatment response in patients with pancreatic neuroendocrine tumors. VEGF pathway SNPs are potentially associated with survival outcomes.

• MeSH
• Progression-Free Survival MeSH
• Pharmacogenomic Testing MeSH
• Protein Kinase Inhibitors administration & dosage   adverse effects   MeSH
• Interleukin-1beta genetics   MeSH
• Polymorphism, Single Nucleotide MeSH
• Kaplan-Meier Estimate MeSH
• Middle Aged MeSH
• Humans MeSH
• Pancreatic Neoplasms drug therapy   genetics   mortality   MeSH
• Neuroendocrine Tumors drug therapy   genetics   mortality   MeSH
• Aged MeSH
• Sunitinib administration & dosage   adverse effects   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase IV MeSH

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.

• MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Survival Rate MeSH
• Pancreatic Neoplasms drug therapy   mortality   pathology   MeSH
• Neuroendocrine Tumors drug therapy   mortality   pathology   MeSH
• Disease-Free Survival MeSH
• Antineoplastic Agents adverse effects   therapeutic use   MeSH
• Aged MeSH
• Sunitinib adverse effects   therapeutic use   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH