177Lu-DOTATATE shows efficacy in both grade 2 high and grade 3 low GEP-NETs


Simron Singh, Canada presenting the data of the NETTER-2 study during the Mini Oral Session 1 at the ESMO Gastrointestinal Cancers Congress 2024 (26-29 June, Munich)

Promising data from a subgroup analysis of the phase III NETTER-2 study support the use of peptide receptor radionuclide therapy in treatment-naïve patients

Peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE (177Lu-DOTATATE) has demonstrated efficacy across grade 2 high-grade 3 low gastroenteropancreatic neuroendocrine tumours (GEP NETs) (Lancet. 2024: S0140-6736(24)00701-3), including tumours of different primary origins in a subgroup analysis of the phase III NETTER-2 study presented at the ESMO Gastrointestinal Cancers Congress 2024 (Munich, 26–29 June) (Abstract 211MO).

In the pre-planned subgroup analysis, the median progression-free survival (mPFS) was longer for the 177Lu-DOTATATE arm versus the high-dose octreotide control arm, regardless of tumour grade (grade 2: 29.0 months versus 13.8 months; grade 3: 22.2 months versus 5.6 months) or primary tumour origin (pancreas: 19.4 months versus 8.5 months; small intestine: 29.0 versus 8.4 months). Objective response rates (ORRs) were also notably higher with 177Lu-DOTATATE compared with control across all subgroups.

ESMO_GI 2024_Garcia Carbonero

Figure. PFS was longer with 177Lu-DOTATATE than with high-dose octreotide in patients with grade 2 high-grade 3 low GEP-NETs in the NETTER-2 study (ESMO Gastrointestinal Cancers Congress 2024, Abstract 211MO)

Currently, first-line therapy for higher grade GEP-NETs consists of cytotoxic chemotherapy, although evidence to support this common practice is rather weak for primary sites other than the pancreas, highlighting a significant unmet need for these patients. Moreover, grade 3 GEP-NETs are a relatively recently defined category of NETs and data on optimal treatment strategies in this setting are lacking. No therapies have been specifically approved for the treatment of grade 3 GEP-NETs and current guidelines recommend treatments based on those for rapidly progressing grade 2 high disease.

Commenting on the subgroup analysis findings, Dr Rocio Garcia-Carbonero from Hospital Universitario Doce de Octubre, Madrid, Spain, notes, “This is a critical study as it is the first randomised controlled trial to assess PRRT and provide specific efficacy data for grade 3 NETs and for treatment-naïve patients.”

The randomised controlled NETTER-2 trial evaluated the efficacy of 177Lu-DOTATATE as first-line treatment in newly diagnosed patients with grade 2 high or grade 3 low (Ki67 10%–55%) well-differentiated GEP-NETs. The primary results, presented earlier this year (J Clin Oncol. 2024;42(3_suppl):LBA588), demonstrated a significantly improved mPFS and increased ORR in patients treated with 177Lu-DOTATATE (n=151) compared with those receiving control (n=75).

Regarding the use of this treatment in the clinic, Garcia-Carbonero remarks, “The activity shown by 177Lu-DOTATATE in the NETTER-2 study is highly clinically relevant and supports its use as a frontline treatment for somatostatin receptor-positive grade 3 low GEP-NETs and maybe selected patients with grade 2 high GEP NETs.” However, she cautions that the NETTER-2 trial does not compare the effectiveness of 177Lu-DOTATATE to the recommended standard treatment for patients with grade 2 or grade 3 GEP-NETs (everolimus, sunitinib or chemotherapy) – a question that ongoing head-to-head studies aim to address. Additionally, there is a need to better understand toxicities associated with 177Lu-DOTATATE and how they may impair further treatments down the line before it can be recommended as the frontline treatment of choice for all patients with grade 2 high-grade 3 low GEP-NETs.

Abstract discussed:

Singh S, et al. First-Line Efficacy of [177Lu]Lu-DOTA-TATE in Patients with Advanced Grade 2 and Grade 3, Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors by Tumor Grade and Primary Origin: Subgroup Analysis of the Phase 3 NETTER-2 Study. ESMO Gastrointestinal Cancers Congress 2024, Abstract 211MO

Mini Oral Session 1, 26.06.2024, h. 16:30 – 18:00, Room 14

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.