177Lu-DOTATATE significantly extends PFS in patients with GEP-NETs, regardless of grade or origin

Results from a subgroup analysis of the NETTER-2 trial support the use of ¹⁷⁷Lu-DOTATATE, a peptide receptor radionuclide therapy, in treatment-naïve patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs), regardless of the tumour grade or origin.

There are currently no standard first-line treatment options for patients with higher grade 2–3, well-differentiated, advanced GEP-NETs. Recently, results from the phase 3 NETTER-2 trial (NCT03972488) showed that ¹⁷⁷Lu-DOTATATE plus octreotide (30 mg) significantly improved progression-free survival (PFS) compared with high dose octreotide (60 mg) in patients with somatostatin receptor-positive, higher grade GEP-NETs [1]. Now, Dr Simron Singh (University of Toronto, Canada) presented results from a pre-planned subgroup analysis of the trial [2].

NETTER-2 randomised 226 participants to first-line treatment with ¹⁷⁷Lu-DOTATATE plus octreotide (n=151) or high dose octreotide alone (control arm, n=75). In the total study population, the median PFS was 22.8 months in the ¹⁷⁷Lu-DOTATATE arm versus 8.5 months in the control arm (HR 0.276; 95% CI 0.182–0.418; P<0.0001) [1].

The subgroup analysis demonstrated a benefit of ¹⁷⁷Lu-DOTATATE both in participants with grade 2 (n=142) or grade 3 (n=79) GEP-NETs: median PFS of 29.0 versus 13.8 months (HR 0.306) and of 22.0 versus 5.6 months (HR 0.266), respectively [2]. In addition, a benefit of ¹⁷⁷Lu-DOTATATE was observed regardless of the primary tumour origin (see Figure). The median PFS in participants with pancreatic NETs (n=123) was 19.4 versus 8.5 months (HR 0.336); in participants with small intestine NETs (n=66) it was 29.0 versus 8.4 months (HR 0.305). Median PFS in participants with other GEP-NETs (n=37) was not shown.

Figure: PFS benefit with ¹⁷⁷Lu-DOTATATE for patients with GEP-NETs [2]



GEP-NETs, gastroenteropancreatic neuroendocrine tumours; PFS, progression-free survival.

Objective response rates for ¹⁷⁷Lu-DOTATATE were 40.4%, 48.1%, 51.2%, and 26.7% in participants with grade 2, grade 3, pancreatic, and small intestine NETs, respectively. The median duration of response was 24.9 months, 19.3 months, 18.4 months, and not yet reached in the respective subgroups.

Based on these results, Dr Singh concluded that “first-line ¹⁷⁷Lu-DOTATATE plus octreotide should be considered a standard-of-care for patients with advanced, well-differentiated, grade 2 or 3, somatostatin receptor-positive GEP-NETs.”

1. Singh S, et al. Lancet. 2024;403(10446):2807-2817.
2. 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. Abstract 211MO, ESMO Gastrointestinal Cancers Congress 2024, 26–29 June, Munich, Germany.

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Posted on 21 August 202421 August 2024