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
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The objective of this study was to investigate and present the early results on the efficacy, safety, and quality of life of 225Ac-DOTATATE targeted alpha therapy (TAT) in patients with advanced, progressive, 177Lu-DOTATATE refractory, and somatostatin receptor (SSTR) expressing metastatic GEP-NETs.
In this prospective study, we recruited patients with metastatic GEP-NETs who were stable or progressive disease on 177Lu-DOTATATE therapy. Systemic TAT using 225Ac-DOTATATE was performed in all the patients with 225Ac-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).
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 177Lu-DOTATATE therapy (14, 44%) or progressive disease on 177Lu-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-225Ac-DOTATATE therapy (P < 0.0001).
Our short-term clinical results indicate 225Ac-DOTATATE TAT as a promising treatment option which adds a new dimension in patients who are refractory to 177Lu-DOTATATE therapy or have reached the maximum prescribed cycles of 177Lu-DOTATATE therapy.
Keywords225Ac-DOTATATE therapy Targeted alpha therapy GEP-NET
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical clearance received Ref. No. IEC-517.
Informed consent obtained from all patients.
This work has not been submitted elsewhere as a full article or has not under consideration to any other journal.
- 1.Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, et al. PROMID Study Group. A placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumour growth in patients with metastatic neuroendocrine midgut tumours: a report from the PROMID Study Group. J Clin Oncol 2009;7:4656–4663.Google Scholar
- 2.Delavault P, Caplin ME, Liyanage N, Blumberg J. The CLARINET study: assessing the effect of lanreotide autogel on tumour progression-free survival in patients with nonfunctioning gastroenteropancreatic neuroendocrine tumours. J Clin Oncol. 2017;30(15_suppl). https://doi.org/10.1200/jco.2012.30.15_suppl.tps4153 Published online January 31, 2017.
- 3.Yao JC, Fazio N, Singh S, Buzzoni R, Carnaghi C, Wolin E, et al. RAD001 in Advanced Neuroendocrine Tumours, Fourth Trial (RADIANT-4) Study Group. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016;387:968–77.CrossRefGoogle Scholar
- 9.Ballal S, Yadav MP, Damle NA, Sahoo RK, Bal C. Concomitant 177Lu-DOTATATE and capecitabine therapy in patients with advanced neuroendocrine tumours: a long-term-outcome, toxicity, survival, and quality-of-life study. Clin Nucl Med. 2017;42:e457–e66. https://doi.org/10.1097/RLU.0000000000001816.CrossRefPubMedGoogle Scholar
- 16.Kratochwil C, Giesel FL, Bruchertseifer F, Mier W, Apostolidis C, Boll R, et al. 213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience. Eur J Nucl Med Mol Imaging. 2014;41:2106–19.CrossRefGoogle Scholar
- 18.Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Publish Date: November 27, 2017.Google Scholar
- 22.Fayers PM, Aaronson NK, Bjordal K. On behalf of the EORTC Quality of Life Group et al. The EORTC QLQ-C30 scoring manual (3rd edition) Brussels: European Organisation for Research and Treatment of Cancer; 2001.Google Scholar
- 24.Bjordal K, Hammerlid E, Ahlner-Elmqvist M, de Graeff A, Boysen M, Evensen JF, et al. Quality of life in head and neck cancer patients: validation of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-H&N35. J Clin Oncol. 1999;17:1008–19.CrossRefGoogle Scholar