1142O - Multivariable analysis of streptozotocin plus 5-fluorouracil and everolimus sequences in advanced pancreatic neuroendocrine tumor patients: The SEQTOR trial (GETNE-1206)

Background

Streptozotocin (STZ) plus 5-Fluorouracil (5-FU) and everolimus are standard treatment options for pancreatic neuroendocrine tumors (panNET). The SEQTOR trial is the first prospective, randomized phase III study that aimed to determine the optimal sequence for these treatments in patients (pts) with advanced panNET.

Methods

Pts received either everolimus (10 mg qd) as first followed by STZ/5-FU (Arm A) or the reverse sequence (Arm B). Eligible pts had confirmed diagnosis of unresectable or metastatic, advanced panNET. Primary endpoint was 12-months progression-free survival rate to 1st treatment (12-m PFS1). Here we report the post hoc multivariable analysis for efficacy endpoints adjusted by treatment arm.

Results

141 pts were randomized; 72 in Arm A and 69 in Arm B. Overall response rate to 1st treatment (ORR1) was superior in STZ/5-FU (11.6% vs 30.3%; p=0.012) at univariable analysis and this benefit had a tendency to be greater in pts with grade 2 tumors at multivariable analysis, having 13 times higher probability of response with STZ/5-FU. STZ/5-FU also had better ORR than everolimus in the 2nd treatment (32.4% vs 9.7%; p=0.035). No significant differences were observed in the 12-m PFS1 (69.5% vs 62.1% in arms A and B, respectively; hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.8-1.8; p=0.431). Overall survival (OS) was worse in patients with a high tumor burden, regardless of treatment arm (HR: 2.3, 95% CI: 1.3-4.2; p=0.004), being an independent prognostic marker. Thirty-four pts were treatment-naive and had an ORR1 of 33.3% and 7.7% for arms A and B, respectively. Treatment-naive pts in arm B had a higher risk of death (HR: 2.7, 95% CI: 1.2-6; p=0.017) when compared to treatment-naive pts in arm A. No differences in OS were seen between arms in pretreated pts.

Conclusions

STZ/5-FU is more effective to obtain treatment responses regardless of sequentiality, especially in pts with grade 2 tumors. Our results suggest that STZ/5-FU may be used as rescue therapy in pts with panNET after progression on 1st line treatments. High tumor burden is an independent prognostic factor, and tumor shrinkage may be a main objective in selected pts.

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.

Legal entity responsible for the study

Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE).

Funding

Novartis awarded a grant to GETNE to cover the costs of the study. The funder did not have a role in designing or conducting the study.

Disclosure

S. Tafuto: Financial Interests, Personal, Advisory Role: Ipsen, Camurus, Novartis, Boehringer, 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: Astra Zeneca, Janssen, Ipsen; Financial Interests, Institutional, Other, Inclusion of patients in 2 phase III studies: MSD; Financial Interests, Institutional, Other, Inclusion of patients in a Phase III study: Bayer, Incyte, Servier, Exelixis Inc., Roche, Taiho; Non-Financial Interests, Personal, Membership or affiliation, Chair of scientific committee: Dutch Cholangio and hepatocellular Carcinoma Group; Non-Financial Interests, Personal, Other, Co-author of the ESMO guideline for biliary tract cancer: ESMO; Non-Financial Interests, Personal, Membership or affiliation, Member of scientific committee: Duthc/Belgian NET society; Non-Financial Interests, Personal, Membership or affiliation: National Guideline committee for biliary tract cancer in the Netherlands; Non-Financial Interests, Personal, Membership or affiliation, Member of the AMMF (patient representative group in the UK for patients with biliary tract cancer) medical advisory board: AMMF. R. Salazar Soler: Financial Interests, Personal, Expert Testimony: Esteve, Laboratorios Servier; Financial Interests, Personal, Advisory Board: GSK, Sanofi Genzyme; Other, Personal, Other, Commercial Medical Education Company owned by wife until december 2023: SACE Medhealth; Other, Personal, Other, Co-administrator and co-owner of this commercial medical education company until April 2022: SACE Medhealth; Non-Financial Interests, Personal, Other, Member of executive committee: TTD; Financial Interests, Personal and Institutional, Coordinating PI: WNT Pharma. All other authors have declared no conflicts of interest.