First-line efficacy of [177Lu]Lu-DOTA-TATE in gastroenteropancreatic neuroendocrine tumors by tumor grade and primary origin: phase 3 NETTER-2 subgroup analysis

MD Simron Singh,; MD Daniel Halperin,; MD Sten Myrehaug,; MD Ken Herrmann,; MD Marianne Pavel,; MD Pamela L. Kunz,; MD Beth Chasen,; MD, PhD Jaume Capdevila,; MD Salvatore Tafuto,; MD Do-Youn Oh,; MD, PhD Changhoon Yoo,; MD Stephen Falk,; MD Thorvardur Halfdanarson,; MD Ilya Folitar,; PhD Yufen Zhang,; Herr, MD, PhD Wouter W. de; MD Diego Ferone

doi:10.1530/endoabs.108.C31

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Endocrine Abstracts (2024) 108 C31 | DOI: 10.1530/endoabs.108.C31

NANETS2024 17th Annual Multidisciplinary NET Medical Symposium NANETS 2024 Clinical - Nuclear Medicine/Interventional Radiology/Imaging (21 abstracts)

First-line efficacy of [177Lu]Lu-DOTA-TATE in gastroenteropancreatic neuroendocrine tumors by tumor grade and primary origin: phase 3 NETTER-2 subgroup analysis

Simron Singh, MD¹, Daniel Halperin, MD², Sten Myrehaug, MD¹, Ken Herrmann, MD³, Marianne Pavel, MD⁴, Pamela L. Kunz, MD⁵, Beth Chasen, MD², Jaume Capdevila, MD, PhD⁶, Salvatore Tafuto, MD⁷, Do-Youn Oh, MD⁸, Changhoon Yoo, MD, PhD⁹, Stephen Falk, MD¹⁰, Thorvardur Halfdanarson, MD¹¹, Ilya Folitar, MD¹², Yufen Zhang, PhD¹³, Wouter W. de Herder, MD, PhD¹⁴ & Diego Ferone MD¹⁵

Author affiliations

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

Background: In the Phase 3 NETTER-2 study (NCT03972488), first-line [¹⁷⁷Lu]Lu-DOTA-TATE (hereafter ¹⁷⁷Lu-DOTATATE) significantly improved median progression-free survival (PFS) by 14 months and increased objective response rate (ORR) by 34% vs high-dose octreotide in patients with advanced, well-differentiated, Grade 2 (G2) and G3, gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This preplanned subgroup analysis examined efficacy by NET grade (G2, G3) and NET origin (pancreas, small intestine [SI]).

Methods: Patients were randomized to 4 cycles of ¹⁷⁷Lu-DOTATATE (4 × 7.4 GBq) + 30 mg octreotide long-acting release (LAR) every 8 weeks (Q8W) during ¹⁷⁷Lu-DOTATATE treatment then Q4W (n = 151), or 60 mg octreotide LAR Q4W (n= 75). Efficacy parameters (PFS, ORR, duration of response [DOR], time to response [TTR]) were centrally assessed (RECIST 1.1).

Results: For PFS and ORR, a clinical benefit in favor of ¹⁷⁷Lu-DOTATATE was evident across subgroups (Table). In the ¹⁷⁷Lu-DOTATATE arm, median PFS was shorter for patients with G3 vs G2 and pancreatic NETs (pNETs) vs SI-NETs. ORR was high in patients with G3 and G2 and higher in pNETs vs SI-NETs. Among 65 patients with complete/partial response to ¹⁷⁷Lu-DOTATATE, median TTR was ~5.8 months (m) for all 4 subgroups, and median DOR (95% confidence interval) was 24.9 m (23.3, not estimable [NE]) in G2 NETs, 19.3 m (17.8, NE) in G3 NETs, 18.4 m (11.3, 23.3) in pNETs and NE for SI-NETs. The low number of responders in the control arm (n = 7) precluded DOR and TTR subgroup analyses.

**Efficacy outcomes by subgroup**
Tumor subgroup	PFS event/n (%)	*Median PFS (95% CI), m**	Responders/n	ORR (95% CI), %
G2: ¹⁷⁷Lu-DOTATATE	29/99 (29.3)	29.0 (21.8, NE)	40/99	40.4 (30.7, 50.7)
G2: Control	25/48 (52.1)	13.8 (8.4, 19.3)	5/48	10.4 (3.5, 22.7)
G3: ¹⁷⁷Lu-DOTATATE	26/52 (50.0)	22.2 (13.9, 27.8)	25/52	48.1 (34.0, 62.4)
G3: Control	21/27 (77.8)	5.6 (3.7, 8.9)	2/27	7.4 (0.9, 24.3)
Pancreas: ¹⁷⁷Lu-DOTATATE	39/82 (47.6)	19.4 (16.6, 24.9)	42/82	51.2 (39.9, 62.4)
Pancreas: Control	27/41 (65.9)	8.5 (3.8, 16.6)	5/41	12.2 (4.1, 26.2)
SI: ¹⁷⁷Lu-DOTATATE	11/45 (24.4)	29.0 (21.8, NE)	12/45	26.7 (14.6, 41.9)
SI: Control	10/21 (47.6)	8.4 (5.4, NE)	1/21	4.8 (0.1, 23.8)
*Kaplan-Meier estimate.

Conclusions: First-line ¹⁷⁷Lu-DOTATATE efficacy was maintained across NET grades (G2, G3) and locations (pancreas, SI). ¹⁷⁷Lu-DOTATATE should be considered a standard of care for this population. Funded by Advanced Accelerator Applications, a Novartis company. Previously presented at ESMO Gastrointestinal Cancers Congress 2024, FPN (Final Publication Number): 211M0, Simron Singh et al. – Reused with permission.

ABSTRACT ID28651