Pharmacogenomic analysis of sunitinib in patients with pancreatic neuroendocrine tumors

Written by N Fazio, Martini JF, Croitoru A et al.

Photo credit: Min Yu (Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC)

Pancreatic neuroendocrine tumors (panNETs) are rare malignancies, however, the incidence appears to be increasing. Unfortunately, most of the treatments available may eventually be associated with either a primary resistance or a progressive loss of antitumor activity. Sunitinib is a TKI that inhibits the VEGFR signalling pathway and is approved for the treatment of progressive, well-differentiated panNETs. Not all patients treated with sunitinib experience benefit, and interpatient variability may be at least in part related with polymorphisms of sunitinib targets.

The latest study published in Future Oncology evaluated potential associations between clinical outcomes and single nucleotide polymorphisms (SNPs), using a subset of patients from the Phase IV trial of sunitinib treatment in patients with panNETs.

Abstract:

Aims: To evaluate associations between clinical outcomes and SNPs in patients with well-differentiated panNETs receiving sunitinib.

Patients & Methods: Kaplan-Meier and Cox proportional hazards models were used to analyse 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 analyse objective response rate (ORR) and genotype associations.

Results: After multiplicity adjustment, progression-free survival and overall survival were not significantly correlated with SNPs; however, a higher ORR was significantly associated with IL1B rs16944 G/A versus G/G (46.4% vs 4.5%; p=0.001).

Conclusions: IL1B SNPs may predict treatment response in patients with panNETs. VEGF pathway SNPs are potentially associated with survival outcomes.

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