1150P - Search for biomarkers to personalize treatment with streptozotocin plus 5-fluorouracil or everolimus in patients with advanced pancreatic neuroendocrine tumors: The randomized phase III SEQTOR trial (GETNE-1206)

Background

Genes involved in transcription and chromatin remodeling (i.e DAXX and ATRX), and tumor suppression (i.e MEN1 and PTEN) are commonly mutated in patients (pts) with pancreatic neuroendocrine tumors (panNETs). Here we report the translational results from the SEQTOR trial that evaluated treatment sequence in panNETs.

Methods

Pts with grade 1/2 advanced panNETs, were randomized to receive everolimus (10 mg per day) at first line, followed by STZ/5-FU at second line (Arm A) or the reverse sequence (Arm B). Paraffin embedded tumor tissue underwent DNA sequencing, using NanoString digital hybridization-detection system. TempOSeq multiomic profile including more than 22.533 genes was performed for 27 pts to classify pts in gene expression subtypes. Primary endpoint, 12-months progression-free survival (PFS) rate, and secondary endpoints, objective response rate (ORR) and overall survival (OS), were correlated with biomarkers.

Results

Mutational analysis was performed in 46 out of 141 pts. MEN1 was mutated in 12 (63%) and 11 (41%) in arms A/B respectively, ATRX in 5 (26%) and 6 (22%), DAXX in 5 (26%) and 5 (19%), and PTEN in 3 (16%) and 3 (11%). Four panNETs gene expression subtypes were obtained from TempOSeq profiling: Insulinoma-like (21%), metastases-like primary (MLP-1; 21%), MLP-2 (21%) and intermediate (37%). Insulinoma subtype had significantly lower risk of PD than other genetic subtypes. OS was not influenced by tumor genetic alterations.

Conclusions

Genetic alterations in the SEQTOR study had similar prevalence than previous reports in pts with panNETs. Pts with insulinoma-like gene expression subtype seem to have lower risk of PD in line with previous observations of good prognosis in this patient subgroup and a watch and wait strategy or less aggressive strategies could be considered for them.

Clinical trial identification

EudraCT 2013-000726-66 NCT02246127.

Editorial acknowledgement

We acknowledge Mfar Clinical Research staff for their assistance in the development of this abstract. We acknowledge La Marató de TV3.

Legal entity responsible for the study

Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE).

Funding

La Marató de TV3 convocatoria 2019 awarded a grant to cover the costs of the study. The funder did not have a role in designing or conducting the study.

Disclosure

R. Salazar Soler: Financial Interests, Personal, Advisory Board: GSK, Sanofi Genzyme, Laboratorios Servier, Esteve; Financial Interests, Personal, Other, Commercial Medical Education Company owned by wife until december 2023: SACE Medhealth; Financial Interests, Personal, Other, Co-administrator and co-owner of this commercial medical education company until April 2022: SACE Medhealth; Financial Interests, Personal, Other, Member of executive committee: TTD; Financial Interests, Personal and Institutional, Coordinating PI: WNT Pharma. S. Tafuto: Financial Interests, Personal, Advisory Role: Ipsen, Camurus, Novartis, Boehringer Ingelheim, Deciphera; Financial Interests, Personal, Research Grant: Ipsen, Camurus, Novartis. A. Teule: Financial Interests, Personal, Other, Speaking, writing, public presentations, advisory service, travel grants: Novartis, Esteve, Pfizer, Adacap, Amgen; Non-Financial Interests, Personal, Membership or affiliation: GETNE, ENETS, ESMO, SEOM, Asociación Española de Genética Humana. H.J. Klumpen: Financial Interests, Institutional, Advisory Board, Member of a single advisory board meeting: AstraZeneca, Janssen, Ipsen; Financial Interests, Institutional, Research Funding, Inclusion of patients in 2 phase III studies: MSD; Financial Interests, Institutional, Research Funding, Inclusion of patients in a Phase III study: Bayer, Incyte, Servier, Exelixis Inc., Roche, Taiho. All other authors have declared no conflicts of interest.