Long-term results and tolerability of tandem peptide receptor radionuclide therapy with 90Y/177Lu-DOTATATE in neuroendocrine tumors with respect to the primary location: a 10-year study

The peptide receptor radionuclide therapy (PRRT) with Y-90 and Lu-177 is a form of molecular targeted therapy for inoperable or disseminated neuroendocrine tumors (NET). The aim of the study was to evaluate clinical results and long-term side effects of tandem Y-90 /Lu-177-DOTATATE therapy in patients with NET. Additionally, we evaluated clinical results with reference to the primary site. 59 patients with disseminated NET were included in the study prospectively. 3-5 cycles of combined 1:1 Y-90/Lu-177-DOTATATE (total injected activity 11.1-16.65 GBq) with mixed amino acids for kidney protection were performed. During a median follow-up of 75.8 months, the PFS was 32.2 months, and the OS was 82 months; 25 patients died. Depending on primary tumor's site, the PFS and the OS for pancreatic NET vs. small bowel, NET vs. large bowel, NET were 30.4 vs. 29.5 vs. 40.3 and 78.9 vs. 58.1 vs. 82.5, respectively. The observed 5-year overall survival was 63%, and a 2-year risk of progression was 39.4%. The following imaging response was observed: CR in 2%, PR in 22%, SD in 65%, and PD in 6% patients. The disease control rate was 89%. The objective response rate was 24%. The PRRT was well tolerated by all patients. One patient (2%) revealed MDS, and one patient (2%) grade 3 nephrotoxicity. No other grade 3 and 4 hematological or renal toxicity was observed. These results indicated the tandem Y-90/Lu-177-DOTATATE therapy for patients with disseminated/inoperable NET as highly effective and safe, considering long-term side effects. In the majority of patients, clinical improvement was observed.