The Safety and Efficacy of the Repeated PRRT with [90Y]Y/[177Lu]Lu-DOTATATE in Patients with NET.

Anna Zemczak,Beata Kos-Kudła,Jolanta Kunikowska,Leszek Królicki,Paweł Gut,Marek Ruchała,Dariusz Pawlak,Maciej Kołodziej,Grzegorz Kamiński,Giuseppe Reimondo

doi:10.1155/2021/6615511

Abstract

Purpose The peptide receptor radionuclide therapy (PRRT) is a treatment option for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours (NETs). The study aims to evaluate the safety, efficacy, and progression-free survival (PFS) of patients after retreatment (R-PRRT) and re-retreatment (RR-PRRT) with tandem isotopes [90Y]Y/[177Lu]Lu-DOTATATE. Material and Methods. Out of 99 treated patients with G1 and G2 NETs, 26 were included in the study and treated with the repeated PRRT (with 5 undergoing the re-repeated PRRT treatment) after an initial positive response to four PRRT cycles and later progression of the disease. [68Ga]Ga-DOTATATE PET/CT and CT/MRI procedures were performed before and after the treatment. Patients were treated with [90Y]Y/[177Lu]Lu-DOTATATE (1 : 1) with mixed amino acid infusion for kidney protection. Toxicity was evaluated using the CTCAE 3.0 criteria. Results The median follow-up was 88 months (the range: 42–164). The median cumulative administered activity was 22.2 GBq (the range: 17.8–30.7 GBq). Myelodysplastic syndrome occurred in one patient (3.8%), and grade 4 renal toxicity was also detected in one patient (3.8%). No other cases of grade 3 or 4 bone marrow and renal toxicity were observed. The median PFS rate was 31 months after the PRRT and 23 months following the R-PRRT. The OS rate from the diagnosis (OS-d) was 109 months and from the start of the PRRT (OS-t)-92.4 months. During the restaging, 3–6 months after the PRRT, PR, SD, and PD were observed in 19.2%, 80.8%, and 0% of the patients, respectively. After the R-PRRT, PR, SD, and PD were observed in 50%, 42.3%, and 7.7% of the patients, respectively. Conclusions The repeated therapy with [90Y]Y/[177Lu]Lu-DOTATATE is safe and effective for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours.

Highlights

SSTRs [1]. e peptide receptor radionuclide therapy (PRRT) has been used to treat neuroendocrine tumours (NETs) for more than 25 years
As the group of patients treated with the RR-PRRT was small, they were not subjected to a detailed analysis, and the results obtained for those patients are not reliable
E median progression-free survival (PFS) after the initial PRRT was 31 months, which was statistically longer than the PFS period after the R-PRRT, which amounted to 23 months (p 0.048) (Figure 2)

Summary

Introduction

SSTRs [1]. e peptide receptor radionuclide therapy (PRRT) has been used to treat NETs for more than 25 years. Once application of amino acid infusion during the PRRT was introduced to the clinical practice, the level of nephrotoxicity was reduced, becoming more common after application of 90Y, or sequential use of 90Y and 177Lu, than in the case of any treatment conducted with 177Lu alone (2.8% vs 1.3 vs 0%, respectively) [9]. Other PRRT-focused studies have confirmed greater nephrotoxicity in patients treated with 90Y than 177Lu [6,7,8, 10]. Grade 3 or 4 bone marrow toxicity developed in 9.5% of cases and occurred more frequently after application of 90Y than 177Lu. Myelodysplastic syndrome occurred in 2.35% of the patients, and leukaemia, in 1.1% [9]

Methods

Results

Conclusion