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

[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 Unpublished/updated data were requested from the investigators of the included publications where needed to provide missing information/enable evaluation of additional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 (I2 >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.