496MO - Final overall survival results from the NICE-NEC trial (GETNE-T1913): A phase II study of nivolumab and platinum-doublet chemotherapy (CT) in untreated advanced G3 neuroendocrine neoplasms (NENs) of gastroenteropancreatic (GEP) or unknown (UK) origin

Background

G3 NENs are aggressive tumors with a median overall survival (OS) of ∼11 months (m) with standard platinum-based front line CT. Their high mutational burden and PD-L1 overexpression position G3 NENs as potential candidates for immunotherapy. The aim of this study was to assess the efficacy of the combination of CT plus Nivolumab (Niv) in patients (pts) with advanced CT-naïve G3 NENs.

Methods

NICE-NEC is an open-label, non-randomized, phase II trial that recruited pts with metastatic or locally advanced unresectable G3 NENs of GEP/UK origin. Pts received Niv 360mg d1, Carboplatin AUC 5 d1, Etoposide 100mg/m2 d1-3 Q3W (up to 6 cycles) followed by Niv 480mg Q4W (up to 24 m). Primary endpoint was 12-m overall survival (OS) rate. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and safety.

Results

From 2019 to 2021, 38 pts were enrolled. Median age was 61 years, 68% male, 89.4% ECOG 0-1, 68.4% were poorly differentiated, 65.8% had Ki67 >55%, 94.7% stage IV at diagnosis, and 74% had ≥2 organs involved. With a median follow-up of 18.6 m (range: 2.2-24.6) for alive pts, ORR was 54.1%, DCR 83.8% and median PFS was 5.7 m (95%CI: 5.1-9). Throughout the study period, 21 (56.8%) pts died. Median OS was 13.9 m (95%CI: 8.3-NR) with an estimated cumulative survival ratio of 53.8% (95%CI: 39.8-72.6) / 44% (95%CI: 30.1-64.2) at 12/18 m. 12 (32.4%) pts were long survivors (OS >18 m). The 12-m OS rate was 46.7% vs 59.3% for Ki-67 ≤55 and >55, respectively (p=0.513); and 58.3% vs 54.7% for well and poorly differentiated, respectively (p=0.773). Median OS was 6.4 m for colorectal, 14.6 m for pancreatic, and not reached for esophago-gastric / small bowel NENs.

Conclusions

The combination of CT plus Niv shows promising activity and prolonged survival benefit in a subset of pts with GEP/UK primary G3 NENs. Randomized trials are warranted to confirm treatment benefit. Ongoing translational studies may help identify predictive/prognostic biomarkers to improve selection of pts most likely to benefit from this treatment strategy.

Clinical trial identification

EudraCT 2019-001546-18; NCT03980925.

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 en Tumores Neuroendocrinos y Endocrinos (GETNE).

Funding

Grupo Español en Tumores Neuroendocrinos y Endocrinos (GETNE) as Sponsor through industry partner Bristol-Myers Squibb (BMS).

Disclosure

J. Capdevila Castillon: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Hudchinson Pharma, ITM, Advanz, Merck Serono, Esteve; Financial Interests, Personal, Advisory Role: Novartis, Pfizer, Ipsen, Exelixis, Bayer, Eisai, Advanced Accelerator Applications, Amgen, Sanofi, Lilly, Hudchinson Pharma, ITM, Advanz, Merck Serono, Esteve; Financial Interests, Personal, Research Grant: Novartis, Pfizer, AstraZeneca, Advanced Accelerator Aplications, Eisai, Amgen, Bayer; Non-Financial Interests, Institutional, Member, Chair of the Spanish Task Force for Neuroendocrine and Endocrine Tumors Group (GETNE); Non-Financial Interests, Institutional, Member, Executive Committee Member of the European Neuroendocrine Tumor Society (ENETS); Non-Financial Interests, Institutional, Member, Treasurer and Track Chair of the rectal cancer working group of the Spanish Multidisciplinary Group of Digestive Cancers (GEMCAD). P. Jimenez-Fonseca: Financial Interests, Personal, Other, Travel grant: IPSEN; Financial Interests, Personal, Advisory Role: AAA; Financial Interests, Personal, Invited Speaker: Sanofi, LEOpharma, HRApharma; Non-Financial Interests, Institutional, Other, membership or affiliation: Seom, Getne, TTD, ENETS. E. Grande: Financial Interests, Personal, Invited Speaker: Adacap, AstraZeneca, Bristol Myers Squibb, Eisai, Eusa Pharma, IPSEN, Janssen, Lilly, Merck KGa, Pfizer, Roche; Financial Interests, Personal, Advisory Board: Astellas, Bayer, MSD, Novartis, Sanofi-Genzyme; Financial Interests, Institutional, Advisory Board: Caris Life Sciences, OncoDNA (Biosequence); Financial Interests, Institutional, Research Grant, Independent research grant: Astellas, AstraZeneca, Lexicon, MTEM/Threshold, Nanostring Technologies, Pfizer, Roche, Merck; Financial Interests, Institutional, Invited Speaker, Independent research grant: Ipsen; Non-Financial Interests, Other, Ad Board member: ENETS. I. Sevilla: Financial Interests, Personal, Advisory Role: Ipsen, Pfizer, Amgen; Financial Interests, Personal, Invited Speaker: Novartis, PharmaMar, Bayer, AAA. T. Alonso-Gordoa: Financial Interests, Personal, Advisory Board: Ipsen, Sanofi, Bayer, Novartis advanced accelerator applications, Lilly, Eisai; Financial Interests, Personal, Invited Speaker: Pfizer, Roche, Janssen-Cilag; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb; Non-Financial Interests, Project Lead: Pfizer, Ipsen. J. Hernando: Financial Interests, Personal, Expert Testimony: Eisai, Ipsen, Novartis, AAA, Angelini, Pfizer, Roche. R. Garcia-Carbonero: Financial Interests, Personal, Advisory Board: AAA, Advanz Pharma, Amgen, Bayer, HMP, Ipsen, Merck, Midatech, MSD, Novartis, Pierre Fabre, Roche, Servier; Financial Interests, Institutional, Research Grant: BMS, MSD, Pfizer; Non-Financial Interests, Leadership Role, Global PI of investigator-initiated clinical trials (Axinet, Nicenec, Pembrola): BMS, MSD, Pfizer; Other, Honoraria received by spouse for advisory board or invited Speaker roles: Abbie, AstraZeneca, Bayer, Boehringer, BMS, Genomica Lilly, MSD, Merck, Novartis, Pfizer, PharmaMar, Roche, Sanofi, Servier, Takeda. All other authors have declared no conflicts of interest.