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Radioligand therapy — personalized treatment for patients with neuroendocrine tumors

Agnieszka Kolasińska-Ćwikła1
DOI: 10.5603/OCP.2021.0043
Affiliations
  1. Klinika Onkologii i Radioterapii, Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie — Państwowy Instytut Badawczy w Warszawie

open access

Ahead of print
REVIEW ARTICLES
Published online: 2022-06-02

Abstract

Over the past 2 decades, radioligand therapy (RLT), previously referred to as peptide receptor radionuclide therapy, has been proven to be an effective and safe therapeutic option in patients with advanced, unresectable, often progressive, well-differentiated neuroendocrine tumors. The NETTER-1 study, the only randomized phase-III trial to date, established RLT with 177Lu-DOTATATE as the “gold standard” in the treatment of metastatic or locally advanced tumors, which are unresectable, well-differentiated with somatostatin receptor (SSTR) expression, and progressive neuroendocrine tumors.

Abstract

Over the past 2 decades, radioligand therapy (RLT), previously referred to as peptide receptor radionuclide therapy, has been proven to be an effective and safe therapeutic option in patients with advanced, unresectable, often progressive, well-differentiated neuroendocrine tumors. The NETTER-1 study, the only randomized phase-III trial to date, established RLT with 177Lu-DOTATATE as the “gold standard” in the treatment of metastatic or locally advanced tumors, which are unresectable, well-differentiated with somatostatin receptor (SSTR) expression, and progressive neuroendocrine tumors.

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Keywords

neuroendocrine tumours (NET); radioligand therapy (RLT); peptide receptor radionuclide therapy (PRRT); somatostatin receptor overexpression

About this article
Title

Radioligand therapy — personalized treatment for patients with neuroendocrine tumors

Journal

Oncology in Clinical Practice

Issue

Ahead of print

Article type

Review paper

Published online

2022-06-02

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153

Article views/downloads

74

DOI

10.5603/OCP.2021.0043

Keywords

neuroendocrine tumours (NET)
radioligand therapy (RLT)
peptide receptor radionuclide therapy (PRRT)
somatostatin receptor overexpression

Authors

Agnieszka Kolasińska-Ćwikła

References (49)
  1. Bodei L, Mueller-Brand J, Baum RP, et al. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2013; 40(5): 800–816.
  2. Hörsch D, Ezziddin S, Haug A, et al. Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: A multi-institutional registry study with prospective follow-up. Eur J Cancer. 2016; 58: 41–51.
  3. Imhof A, Brunner P, Marincek N, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol. 2011; 29(17): 2416–2423.
  4. Krenning EP, Kooij PP, Bakker WH, et al. Radiotherapy with a radiolabeled somatostatin analogue, [111In-DTPA-D-Phe1]-octreotide. A case history. Ann N Y Acad Sci. 1994; 733: 496–506.
  5. Krenning EP, de Jong M, Kooij PP, et al. Radiolabelled somatostatin analogue(s) for peptide receptor scintigraphy and radionuclide therapy. Ann Oncol. 1999; 10 Suppl 2: S23–S29.
  6. Kwekkeboom DJ, de Herder WW, Kam BL, et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008; 26(13): 2124–2130.
  7. Hope TA, Bodei L, Chan JA, et al. NANETS/SNMMI Consensus Statement on Patient Selection and Appropriate Use of Lu-DOTATATE Peptide Receptor Radionuclide Therapy. J Nucl Med. 2020; 61(2): 222–227.
  8. Krenning EP, Kooij PP, Bakker WH, et al. Radiotherapy with a radiolabeled somatostatin analogue, [111In-DTPA-D-Phe1]-octreotide. A case history. Ann N Y Acad Sci. 1994; 733: 496–506.
  9. Bodei L, Cremonesi M, Grana CM, et al. Peptide receptor radionuclide therapy with ¹⁷⁷Lu-DOTATATE: the IEO phase I-II study. Eur J Nucl Med Mol Imaging. 2011; 38(12): 2125–2135.
  10. Bushnell DL, O'Dorisio TM, O'Dorisio MS, et al. 90Y-edotreotide for metastatic carcinoid refractory to octreotide. J Clin Oncol. 2010; 28(10): 1652–1659.
  11. Cwikla JB, Sankowski A, Seklecka N, et al. Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study. Ann Oncol. 2010; 21(4): 787–794.
  12. Khan S, Krenning EP, van Essen M, et al. Quality of life in 265 patients with gastroenteropancreatic or bronchial neuroendocrine tumors treated with [177Lu-DOTA0,Tyr3]octreotate. J Nucl Med. 2011; 52(9): 1361–1368.
  13. Bodei L, Kidd M, Paganelli G, et al. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors. Eur J Nucl Med Mol Imaging. 2015; 42(1): 5–19.
  14. Kwekkeboom DJ, Krenning EP. Peptide Receptor Radionuclide Therapy in the Treatment of Neuroendocrine Tumors. Hematol Oncol Clin North Am. 2016; 30(1): 179–191.
  15. Strosberg J, El-Haddad G, Wolin E, et al. NETTER-1 Trial Investigators. Phase 3 Trial of Lu-Dotatate for Midgut Neuroendocrine Tumors. N Engl J Med. 2017; 376(2): 125–135.
  16. Strosberg J, Caplin M, Kunz P, et al. 177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021; 22(12): 1752–1763.
  17. Salazar R, Wiedenmann B, Rindi G, et al. ENETS 2011 Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Tumors: an update. Neuroendocrinology. 2012; 95(2): 71–73.
  18. Kvols LK, Brendtro KL. North American Neuroendocrine Tumor Society (NANETS). The North American Neuroendocrine Tumor Society (NANETS) guidelines: mission, goals, and process. Pancreas. 2010; 39(6): 705–706.
  19. Durante C, Boukheris H, Dromain C, et al. Prognostic factors influencing survival from metastatic (stage IV) gastroenteropancreatic well-differentiated endocrine carcinoma. Endocr Relat Cancer. 2009; 16(2): 585–597.
  20. Desai H, Borges-Neto S, Wong TZ. Molecular Imaging and Therapy for Neuroendocrine Tumors. Curr Treat Options Oncol. 2019; 20(10): 78.
  21. Baum RP, Prasad V. Monitoring Treatment. In: Cook GJR, Maisey MN, Britton KE, Chengazi AV. ed. Clinical Nuclear Medicine, 4th ed. Hodder Arnold, London 2006: 57–78.
  22. Chan DLh, Pavlakis N, Schembri GP, et al. Dual Somatostatin Receptor/FDG PET/CT Imaging in Metastatic Neuroendocrine Tumours: Proposal for a Novel Grading Scheme with Prognostic Significance. Theranostics. 2017; 7(5): 1149–1158.
  23. Abdulrezzak U, Kurt YK, Kula M, et al. Combined imaging with 68Ga-DOTA-TATE and 18F-FDG PET/CT on the basis of volumetric parameters in neuroendocrine tumors. Nucl Med Commun. 2016; 37(8): 874–881.
  24. Graf J, Pape UF, Jann H, et al. Prognostic Significance of Somatostatin Receptor Heterogeneity in Progressive Neuroendocrine Tumor Treated with Lu-177 DOTATOC or Lu-177 DOTATATE. Eur J Nucl Med Mol Imaging. 2020; 47(4): 881–894.
  25. Puranik AD, Dromain C, Fleshner N, et al. Target Heterogeneity in Oncology: The Best Predictor for Differential Response to Radioligand Therapy in Neuroendocrine Tumors and Prostate Cancer. Cancers (Basel). 2021; 13(14).
  26. Esser JP, Krenning EP, Teunissen JJ, et al. Comparison of [(177) Lu-DOTA(0), Tyr(3)] octreotate and [(177)Lu-DOTA(0), Tyr(3)]octreotide: which peptide is preferable for PRRT? Eur J Nucl Med Mol Imaging. 2006; 33(11): 1346–1351.
  27. Garkavij M, Nickel M, Sjögreen-Gleisner K, et al. 177Lu-[DOTA0,Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: Analysis of dosimetry with impact on future therapeutic strategy. Cancer. 2010; 116(4 Suppl): 1084–1092.
  28. Kwekkeboom DJ, Bakker WH, Kam BL, et al. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA0,Tyr3]octreotate. Eur J Nucl Med Mol Imaging. 2003; 30(3): 417–422.
  29. Brabander T, van der Zwan WA, Teunissen JJM, et al. Long-Term Efficacy, Survival, and Safety of [Lu-DOTA,Tyr]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors. Clin Cancer Res. 2017; 23(16): 4617–4624.
  30. Strosberg J, Wolin E, Chasen B, et al. First update on overall survival, progression-free survival, and health-related time-to-deterioration quality of life from the NETTER-1 study: 177Lu-Dotatate vs. high dose octreotide in progressive midgut neuroendocrine tumors. J Clin Oncol. 2018; 36(15_suppl): 4099–4099.
  31. Strosberg J, Wolin E, Chasen B, et al. NETTER-1 Study Group. Health-Related Quality of Life in Patients With Progressive Midgut Neuroendocrine Tumors Treated With Lu-Dotatate in the Phase III NETTER-1 Trial. J Clin Oncol. 2018; 36(25): 2578–2584.
  32. Strosberg JR, Srirajaskanthan R, El-Haddad G, et al. Symptom Diaries of Patients with Midgut Neuroendocrine Tumors Treated with Lu-DOTATATE. J Nucl Med. 2021 [Epub ahead of print].
  33. Garske-Román U, Sandström M, Fröss Baron K, et al. Prospective observational study of Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity. Eur J Nucl Med Mol Imaging. 2018; 45(6): 970–988.
  34. Garske-Román U, Sandström M, Fröss Baron K, et al. Prospective observational study of Lu-DOTA-octreotate therapy in 200 patients with advanced metastasized neuroendocrine tumours (NETs): feasibility and impact of a dosimetry-guided study protocol on outcome and toxicity. Eur J Nucl Med Mol Imaging. 2018; 45(6): 970–988.
  35. Ezziddin S, Attassi M, Yong-Hing CJ, et al. Predictors of long-term outcome in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors after peptide receptor radionuclide therapy with 177Lu-octreotate. J Nucl Med. 2014; 55(2): 183–190.
  36. Ezziddin S, Meyer C, Kahancova S, et al. 90Y Radioembolization after radiation exposure from peptide receptor radionuclide therapy. J Nucl Med. 2012; 53(11): 1663–1669.
  37. Sansovini M, Severi S, Ianniello A, et al. Long-term follow-up and role of FDG PET in advanced pancreatic neuroendocrine patients treated with Lu-D OTATATE. Eur J Nucl Med Mol Imaging. 2017; 44(3): 490–499.
  38. Clement D, Navalkissoor S, Srirajaskanthan R, et al. Efficacy and safety of 177Lu-DOTATATE in patients (pts) with advanced pancreatic neuroendocrine tumors (pNETs): Data from the NETTER-R international, retrospective registry. J Clin Oncol. 2021; 39(15_suppl): 4116–4116.
  39. Carlsen EA, Fazio N, Granberg D, et al. Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: a multicenter cohort study. Endocr Relat Cancer. 2019; 26(2): 227–239.
  40. Thang SP, Lung MS, Kong G, et al. Peptide receptor radionuclide therapy (PRRT) in European Neuroendocrine Tumour Society (ENETS) grade 3 (G3) neuroendocrine neoplasia (NEN) - a single-institution retrospective analysis. Eur J Nucl Med Mol Imaging. 2018; 45(2): 262–277.
  41. Nicolini S, Severi S, Ianniello A, et al. Investigation of receptor radionuclide therapy with Lu-DOTATATE in patients with GEP-NEN and a high Ki-67 proliferation index. Eur J Nucl Med Mol Imaging. 2018; 45(6): 923–930.
  42. Zhang J, Kulkarni HR, Singh A, et al. Peptide Receptor Radionuclide Therapy in Grade 3 Neuroendocrine Neoplasms: Safety and Survival Analysis in 69 Patients. J Nucl Med. 2019; 60(3): 377–385.
  43. Bison SM, Konijnenberg MW, Melis M, et al. Peptide receptor radionuclide therapy using radiolabeled somatostatin analogs: focus on future developments. Clin Transl Imaging. 2014; 2: 55–66.
  44. van Essen M, Krenning EP, Kam BL, et al. Report on short-term side effects of treatments with 177Lu-octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2008; 35(4): 743–748.
  45. Claringbold PG, Price RA, Turner JH. Phase I-II study of radiopeptide 177Lu-octreotate in combination with capecitabine and temozolomide in advanced low-grade neuroendocrine tumors. Cancer Biother Radiopharm. 2012; 27(9): 561–569.
  46. Claringbold PG, Turner JH. Pancreatic Neuroendocrine Tumor Control: Durable Objective Response to Combination 177Lu-Octreotate-Capecitabine-Temozolomide Radiopeptide Chemotherapy. Neuroendocrinology. 2016; 103(5): 432–439.
  47. Nicolini S, Bodei L, Bongiovanni A, et al. Combined use of 177Lu-DOTATATE and metronomic capecitabine (Lu-X) in FDG-positive gastro-entero-pancreatic neuroendocrine tumors. Eur J Nucl Med Mol Imaging. 2021; 48(10): 3260–3267.
  48. Kolasinska-Ćwikła A, Nowicki ML, Zrajkowska A, et al. High efficacy of combined PRRT and CAPTEM therapy based on objective response rate (RECIST) in patients with pancreatic and midgut neuroendocrine tumors (NET) ENETS Annual Congress Barcelona, 2021.
  49. Zrajkowska A, Kolasinska-Ćwikła A, Nowicki M, Pałucki J, Nowicka G, Sekelcka N, Ćwikła. Low rate of toxicity of combined PRRT and CAPTEM therapy in patients with advanced, non resectable, progressive pancreatic and midgut neuroendocrine tumors (NET) ENETS Annual Congress Barcelona, 2021.

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