1178P Impact of comprehensive genomics profiling on treatment management of patients with advanced neuroendocrine neoplasms

Abstract

Molecular genomic analyses are widely used in oncology but experience in advanced neuroendocrine neoplasms (NENs) is still limited. We have analyzed the sensibility to detect genomic aberrations in advanced NENs and the potential impact in the treatment decision process. We selected the last correlative 100 patients with advanced NENs in which next-generation sequencing (NGS) analyses were performed. Two different NGS techniques were used on formalin fixed paraffin embedded archival tumor samples: amplicon-seq for detection of DNA mutations and nanostring n-counter for fusions and copy number alterations. We analyzed 37 G1/2 gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), 30 G3 GEP NENs, 21 medullary thyroid cancers (MTC) and 12 G1/G2 NETs of other locations. Genomic alterations were identified in 81.5% of G3 NENs including potentially targetable mutations in KRAS (50%), BRAF (27%), FGFR1 (7%), AKT1/2 (6%), BRCA2 (3%) and ERBB3 (3%). Mutations in RET were detected in 48% of MTC. However, few genomic mutations were identified in G1/G2 NETs (GEP & others) suitable to be treated with targeted agents, including KRAS (6%), FGFR3 (4%), and 1 reported mutation (2%) in each of the following genes of particular interest: FGFR2, ERBB2, PIK3CA and NRAS. NGS analyses may open new treatment options in advanced G3 NENs and are also mandatory upfront in advanced MTC to guide treatment with selective RET inhibitors in current development. However, the rentability of NGS in G1/G2 NETs is clearly lower and should be used in refractory setting or for investigational purposes.