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Endocrine Abstracts (2024) 99 OC7.2 | DOI: 10.1530/endoabs.99.OC7.2

ECE2024 Oral Communications Oral Communications 7: Endocrine-related Cancer (6 abstracts)

[177Lu]Lu-DOTA-TATE in newly diagnosed patients with advanced grade 2 and grade 3, well-differentiated gastroenteropancreatic neuroendocrine tumors: Primary analysis of the phase 3 randomized NETTER-2 study

Diego Ferone 1 , Daniel Halperin 2 , Sten Myrehaug 3 , Ken Herrmann 4,5 , Marianne Pavel 6 , Pamela Kunz 7 , Beth Chasen 2 , Jaume Capdevila 8 , Salvatore Tafuto 9 , Do-Youn Oh 10 , Changhoon Yoo 11 , Stephen Falk 12 , Thorvardur R Halfdanarson 13 , Ilya Folitar 14 , Yufen Zhang 15 , Paola Santoro 15 , Paola Aimone 14 , Wouter W de Herder 16 & Simron Singh 3


1IRCCS Policlinico San Martino and DiMI, University of Genova, Endocrinology, Genova, Italy; 2MD Anderson Cancer Center, Houston, United States; 3University of Toronto, Toronto, Canada; 4National Center for Tumor Diseases (NCT), Heidelberg, Germany; 5University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Department of Nuclear Medicine, Essen, Germany; 6Uniklinikum Erlangen, Friedrich Alexander University Erlangen-Nuernberg, Erlangen, Germany; 7Yale School of Medicine, Yale University, New Haven, United States; 8Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; 9Oncologia Clinica e Sperimentale Sarcomi e Tumori Rari, Istituto Nazionale Tumori IRCCS, Naples, Italy; 10Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea, Rep. of South; 11Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, Rep. of South; 12Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom; 13Mayo Clinic, Rochester, United States; 14Novartis Pharma AG, Basel, Switzerland; 15Novartis Pharmaceuticals Corp, East Hanover, United States; 16Erasmus MC, Rotterdam, Netherlands


Background: There is no universally accepted first-line (1L) therapy for higher grade, well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The Phase 3 NETTER-2 study (NCT03972488) evaluated [177 Lu]Lu-DOTA-TATE (hereafter177 Lu-DOTATATE) as 1L treatment in patients with grade (G)2 and G3 advanced GEP-NETs. This is the first trial to assess 1L radioligand therapy (RLT) in any solid tumor.

Methods: Eligible patients were newly diagnosed with somatostatin receptor-positive high G2 or G3 (Ki-67 ≥10% and ≤55%) advanced GEP-NETs within the last 6 months prior to enrollment. Patients were randomized (2:1) to receive 4 cycles of 177 Lu-DOTATATE (4 × 7.4 GBq) plus 30 mg octreotide long-acting release (LAR) at 8-weekly intervals during 177 Lu-DOTATATE treatment then every 4 weeks (177 Lu-DOTATATE arm), or 60 mg octreotide LAR every 4 weeks (control arm), stratified by grade (G2 vs G3) and tumor origin (pancreas vs other). The primary endpoint was progression-free survival (PFS), centrally assessed using RECIST 1.1. Objective response rate (ORR) was a key secondary endpoint.

Results: Overall, 226 patients were randomized to 177 Lu-DOTATATE (n=151) or control (n=75). Most tumors originated in the pancreas (54.4%) or small intestine (29.2%); G3 tumors were reported in 35.0% of patients. Median cumulative dose of 177 Lu-DOTATATE was 29.2 GBq, with 87.8% of patients receiving all 4 doses. Median PFS (95% confidence interval [CI]) was significantly prolonged by ~14.3 months from 8.5 months (7.7, 13.8) in the control arm to 22.8 months (19.4, not estimable) in the 177 Lu-DOTATATE arm; stratified hazard ratio 0.276 (95% CI: 0.182, 0.418; P<0.0001). The ORR was significantly higher in the 177 Lu-DOTATATE arm (43.0%) vs the control arm (9.3%); stratified odds ratio 7.81 (95% CI: 3.32, 18.4; P<0.0001). PFS and ORR results were consistent across all pre-specified demographic and prognostic subgroups. Among adverse events of special interest to RLT, G3/4 leukopenia, anemia and thrombocytopenia occurred in ≤3 patients each in the 177 Lu-DOTATATE arm. One case of myelodysplastic syndrome was reported (177 Lu-DOTATATE arm).

Conclusion: 177 Lu-DOTATATE significantly prolonged PFS and demonstrated a clinically meaningful ORR, vs high-dose octreotide LAR, in patients with newly diagnosed advanced G2 and G3 GEP-NETs. Safety was in line with the established profile of 177 Lu-DOTATATE. This is the first randomized study to demonstrate efficacy of RLT as first-line treatment in any solid tumor and will change clinical practice. © 2024 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2024 Gastrointestinal Cancers Symposium. All rights reserved.

Volume 99

26th European Congress of Endocrinology

Stockholm, Sweden
11 May 2024 - 14 May 2024

European Society of Endocrinology 

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