# Systematic review and meta‐analysis of the efficacy and safety of [177 Lu]Lu‐edotreotide ([177 Lu]Lu‐DOTATOC) for the treatment of neuroendocrine tumors

## TL;DR

This study reviews and analyzes the effectiveness and safety of [177Lu]Lu-edotreotide for treating neuroendocrine tumors, showing it is effective and well-tolerated, especially for gastro-enteropancreatic tumors.

## Contribution

The first meta-analysis of [177Lu]Lu-edotreotide's efficacy and safety in neuroendocrine tumor patients.

## Key findings

- Patients with gastro-enteropancreatic NETs had better outcomes than those with all NETs in terms of response rates and survival.
- High disease control rates and median progression-free survival were observed, indicating effective disease stabilization.
- Grade 3/4 toxicities were rare, suggesting [177Lu]Lu-edotreotide is generally well tolerated.

## Abstract

[177Lu]Lu‐edotreotide is a radiopharmaceutical therapy (RPT) targeting somatostatin receptors, which are commonly overexpressed on neuroendocrine tumors (NETs). This systematic literature review and meta‐analysis describes the efficacy and safety of [177Lu]Lu‐edotreotide in patients with NETs. To date, there has been no meta‐analysis of data for this specific RPT. PubMed, EMBASE, Cochrane databases, and abstracts from select congresses were searched for eligible studies (February/October 2024). Meta‐analysis was performed using fixed and random‐effects models. The primary objective was to evaluate the efficacy of [177Lu]Lu‐edotreotide in terms of objective response rate (ORR; complete + partial response) in the subgroup of patients with gastro‐enteropancreatic NETs (GEP‐NETs) and those with any NETs, irrespective of origin (All‐NETs). Secondary outcomes included disease control rate (DCR; best overall response of complete response + partial response + stable disease), median progression‐free survival (mPFS), and median overall survival (mOS). Unpublished/updated data were requested from the investigators of the included publications where needed to provide missing information/enable evaluation of additional outcomes. Safety/tolerability data for [177Lu]Lu‐edotreotide were also reviewed. Eight eligible studies were identified for inclusion in the meta‐analysis, all in the advanced disease setting (5/8 included patients with progressive NETs). Most patients had grade 1/2 NETs (grade 1: 11%–63%; 2: 30%–79%; 3: 4%–11%). Updated data were provided for four of these studies. Overall, ORR and DCR were reported in six studies (GEP‐NETs, n = 222; All‐NETs, n = 423), mPFS in five studies (GEP‐NETs, n = 294; All‐NETs, n = 267), and mOS in six studies (GEP‐NETs, n = 256; All‐NETs, n = 408). Meta‐analysis revealed consistently high heterogeneity (I
2 >70%) across outcomes/patient populations. Patients with GEP‐NETs appeared to have better outcomes than those with All‐NETs in terms of ORR (34% vs. 19%), DCR (78% vs. 57%), mPFS (24.9 vs. 18.6 months), and mOS (44.8 vs. 39.1 months), respectively. Safety/tolerability data were inconsistently reported, but grade 3/4 toxicities were rarely noted during [177Lu]Lu‐edotreotide treatment. These results support the effectiveness and safety of [177Lu]Lu‐edotreotide as a treatment for patients with advanced NETs and suggest a potentially more favorable prognosis for those with GEP‐NETs than for the broader All‐NETs population. However, these results should be interpreted with caution due to the high level of heterogeneity. Encouraging ORRs and high DCRs were noted, indicating that [177Lu]Lu‐edotreotide effectively stabilized disease in most patients. Although safety/tolerability data were inconsistently published across studies, [177Lu]Lu‐edotreotide was generally well tolerated. Overall, these findings suggest that the efficacy and safety of [177Lu]Lu‐edotreotide are in line with those reported for other RPTs in similar clinical settings.

Clinical Trial Registration: PROSPERO 2024 CRD42024518028.