Genetic tumor and blood profiling in the randomised controlled phase III COMPOSE trial comparing 177Lu-edotreotide and best standard of care for well-differentiated aggressive grade 2/3 gastroenteropancreatic neuroendocrine tumors

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Introduction: COMPOSE is a randomised, controlled, open-label, Phase III trial in patients with well-differentiated aggressive G2/G3 (Ki-67 index 15−55%), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). 177Lu-edotreotide targeted radionuclide therapy (TRT) will be compared with best standard of care (CAPTEM, FOLFOX or everolimus). Therapeutic strategies for high grade GEP-NETs demonstrate variable outcomes and currently there is a lack of tools to predict TRT efficacy and disease progression. Genetic profiling analysis is proposed to address this need.

Aim(s): Applying a multiomics, integrative, systemic approach, we aim to identify genetic predictive and prognostic markers to improve understanding of tumor progression and TRT responses and to guide individualised treatment of NETS.

Materials and methods: The genetic signatures of GEP-NETs at time of diagnosis will be analysed by DNA whole exome sequencing to understand predisposition and mutational drivers. Differential mRNA expression in solid tumors and blood samples (before, during treatment, at disease progression) will be sequenced to identify relevant genomic and gene expression features with a focus on suppressive/activating genetic traits and comparison of treatments.

Conference:

Presenting Author:

Authors: Capdevila J, Halfdanarson T, Halperin D, Herrmann K, Kong G,

Keywords: gastroenteropancreatic neuroendocrine tumor, targeted radionuclide therapy, bioinformatics, gene expression,