Broadening horizons with 225Ac-DOTATATE targeted alpha therapy for gastroenteropancreatic neuroendocrine tumour patients stable or refractory to 177Lu-DOTATATE PRRT: first clinical experience on the efficacy and safety

Purpose The objective of this study was to investigate and present the early results on the efficacy, safety, and quality of life of Ac-225-DOTATATE targeted alpha therapy (TAT) in patients with advanced, progressive, Lu-177-DOTATATE refractory, and somatostatin receptor (SSTR) expressing metastatic GEP-NETs. Methods In this prospective study, we recruited patients with metastatic GEP-NETs who were stable or progressive disease on Lu-177-DOTATATE therapy. Systemic TAT using Ac-225-DOTATATE was performed in all the patients with Ac-225-DOTATATE (100 kBq/kg body weight) at an interval of 8 weeks. The primary end point was to assess the objective response (measured by RECIST 1.1 and functional M.D. Anderson criteria). The secondary end points included biochemical response assessment as per the Italian Trials in Medical Oncology (ITMO), adverse event profile as per CTCAE v5.0, and clinical response assessment by the quality of life (assessed with EORTC QLQ-GI.NET21 patient-based questionnaire). Results Between April 2018 and March 2019, 32 patients (17 females, 15 males, mean age 52 +/- 9.2 years, 35-72 years) with either stable disease after completing Lu-177-DOTATATE therapy (14, 44%) or progressive disease on Lu-177-DOTATATE therapy (18, 56%) were included in the study. The morphological response was assessed in 24/32 patients that revealed partial remission in 15 and stable disease in 9. There was no documented disease progression or deaths in the median follow-up of 8 months (range 2-13 months). There was a significant decrease in the plasma chromogranin level post-Ac-225-DOTATATE therapy (P < 0.0001). Conclusion Our short-term clinical results indicate Ac-225-DOTATATE TAT as a promising treatment option which adds a new dimension in patients who are refractory to Lu-177-DOTATATE therapy or have reached the maximum prescribed cycles of Lu-177-DOTATATE therapy.