Molecular Correlation of the Activity of Evofosfamide (EVO) in Combination with Sunitinib (SUN) in Pancreatic Neuroendocrine Tumors (pNETs) in the SUNEVO GETNE Trial
Introduction: MEN1, DAXX, ATRX, and PI3K/AKT/mTOR pathway genes are frequently mutated in pNETs. Sunitinib is approved and widely used in the metastatic setting but unfortunately, no validated predictive biomarker has been identified to guide therapy yet. The SUNEVO phase II trial of the Spanish Task Force Group for Neuroendocrine and Endocrine Tumours (GETNE) trial combined the pro-drug of EVO under SUN-induced hypoxic conditions.
Aim(s): We performed an exploratory analysis aimed to identify somatic mutations associated with the clinical benefit of pNET patients treated with SUN+EVO combination.
Materials and methods: Seventeen treatment-naïve pts with pNETS were included in the SUNEVO trial, and 4 (23.5%) achieved a partial response (by RECIST 1.1). Tumor DNA from 10 FFPE tumor samples were successfully sequenced with an enrichment panel (Nimblegen, Roche) including 42 cancer-related genes and TERT promoter region. Median coverage was 793x. Coding non-synonymous and loss-of-function variants were considered for the analysis. Final analysis included tumor samples from the 10 patients with NGS results.
Conference: 17th Annual ENETSConcerence (2020)
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