Efficiency and Safety of Targeted Alpha Therapy in Metastatic Neuroendocrine Tumors

Abstract

Purpose Despite the effectiveness of 177Lu-based peptide receptor radionuclide therapy in treating metastatic neuroendocrine tumors (NETs), disease progression posttreatment remains a significant challenge. Targeted alpha therapy (TAT) has emerged as a promising option for patients experiencing such progression. This study aims to assess the therapeutic efficiency and toxicity of TAT in patients with metastatic NET through a meta-analysis. Patients and Methods We conducted a comprehensive search of PubMed, Embase, Cochrane Library, and CINAHL using relevant keywords. The analysis focused on the pooled proportions of objective response rate (ORR) and disease control rate (DCR) to determine therapeutic efficiency. We also evaluated the incidence of serious hematologic and renal adverse events (grade 3 or 4) to assess toxicity. A subgroup analysis was performed to identify factors influencing therapeutic outcomes. Results Our meta-analysis included 7 studies comprising 162 patients. The results showed that TAT achieved ORR of 49.5% (95% confidence interval [CI]: 41.7%–57.4%) and DCR of 87.0% (95% CI: 72.1%–96.8%). The incidences of hematologic and renal toxicities were low, at 2.1% (95% CI: 0.5%–5.5%) and 3.4% (95% CI: 1.2%–7.3%), respectively. Subgroup analysis indicated consistent therapeutic efficiency across different variables, including prior 177Lu-based peptide receptor radionuclide therapy treatment, 225Ac-based TAT, absence of radiosensitizer, and methods of response evaluation, with ORR ranging from 46.6% to 57.1% and DCR from 82.0% to 91.5%. Conclusions TAT is an effective treatment for metastatic NET, demonstrating substantial disease control and response rates with minimal toxicity. These findings suggest that TAT is a viable therapeutic alternative for patients with metastatic NET.