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

Abstract [ 177 Lu]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 [ 177 Lu]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 [ 177 Lu]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 Unpublished/updated data were requested from the investigators of the included publications where needed to provide missing information/enable evaluation of additional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 [ 177 Lu]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 [ 177 Lu]Lu‐edotreotide treatment. These results support the effectiveness and safety of [ 177 Lu]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 [ 177 Lu]Lu‐edotreotide effectively stabilized disease in most patients. Although safety/tolerability data were inconsistently published across studies, [ 177 Lu]Lu‐edotreotide was generally well tolerated. Overall, these findings suggest that the efficacy and safety of [ 177 Lu]Lu‐edotreotide are in line with those reported for other RPTs in similar clinical settings. Clinical Trial Registration : PROSPERO 2024 CRD42024518028.