Efficacy and safety of (177)Lu-DOTATATE targeted therapy in advanced/metastatic pulmonary neuroendocrine tumors: A systematic review and meta-analysis

OBJECTIVE: To perform a meta-analysis of the efficacy and safety about (177)Lu-DOTATATE therapy for advanced/metastatic pNETs based on the current clinical evidence. METHODS: This systematic review follows the PRISMA guideline. Search PubMed, Medline, EMBASE and CNKI, VIP, Wanfang databases, from establishment to June 2022, on the study of (177)Lu-DOTATATE for advanced/metastatic pNETs, the primary endpoint was to evaluate the treatment effect through DRRs and DCRs. Secondary endpoint included assessment of OS, PFS, and treatment-related adverse events across all studies. Two researchers conducted literature screening, data extraction and quality evaluation according to the inclusion and exclusion criteria. Meta-analysis was performed using stata16.0 software, and the data were merged and displayed using forest graphs. RESULTS: A total of 5 studies, 174 patients, on (177)Lu-DOTATATE for advanced/metastatic pNETs were included. The pools of DRRs and DCRs were 24% (95% CI: 15%~32%) and 77% (95% CI: 62%~92%), respectively. The pool of OS was 48.78 months (95% CI: 41~56.57 months) and the pool of PFS was 21.59 months (95% CI: 17.65~25.53 months). In all studies, the most common side effect of treatment was hematological toxicity. In 174 patients, hematological toxicity of grade III accounted for 4.0% (7/174), and only 4.0% (7/174) and 1.0% (2/174) of patients had mild nephrotoxicity and hepatotoxicity. Gastrointestinal adverse reactions in 3% (6/174), nausea in 2% (3/174), superior vena cava occlusion in 0.5% (1/174). CONCLUSION: (177)Lu-DOTATATE is effective and safe for advanced/metastatic pNETs, which can delay the progression of the disease, may improve patients’ survival, and has low treatment-related toxicity and high safety. However, its efficacy and safety need to be further evaluated in high-quality, multicenter randomized controlled trials in the future. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022344436.