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Phase II trial demonstrates the efficacy and safety of individualized, dosimetry-based 177Lu-DOTATATE treatment of NET patients

Sundlöv, Anna LU orcid ; Gleisner, Katarina Sjögreen LU ; Tennvall, Jan LU ; Ljungberg, Michael LU ; Warfvinge, Carl Fredrik LU ; Holgersson, Kajsa ; Hallqvist, Andreas ; Bernhardt, Peter and Svensson, Johanna (2022) In European Journal of Nuclear Medicine and Molecular Imaging 49(11). p.3830-3840
Abstract

Purpose: Radionuclide therapy with 177Lu-DOTATATE is well established for patients with advanced somatostatin receptor–positive neuroendocrine tumors with a standard schedule of 7.4 GBq at four occasions. However, this approach does not consider individual variability affecting the tumor radiation dose or dose to organs at risk. Therefore, it is important to assess more personalized strategies. The aim of this phase II trial was to evaluate individualized 177Lu-DOTATATE for which the number of cycles varied based on renal dosimetry. Methods: Patients were eligible if they had a progressive, somatostatin receptor–positive neuroendocrine tumor with a Ki 67 labeling index < 20%. They received cycles of 7.4 GBq of... (More)

Purpose: Radionuclide therapy with 177Lu-DOTATATE is well established for patients with advanced somatostatin receptor–positive neuroendocrine tumors with a standard schedule of 7.4 GBq at four occasions. However, this approach does not consider individual variability affecting the tumor radiation dose or dose to organs at risk. Therefore, it is important to assess more personalized strategies. The aim of this phase II trial was to evaluate individualized 177Lu-DOTATATE for which the number of cycles varied based on renal dosimetry. Methods: Patients were eligible if they had a progressive, somatostatin receptor–positive neuroendocrine tumor with a Ki 67 labeling index < 20%. They received cycles of 7.4 GBq of 177Lu-DOTATATE at 10 ± 2-week intervals until a predefined radiation dose to the kidneys was reached. The primary endpoint was objective tumor response (RECIST v 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity (CTCAE v. 4.0). Results: Ninety-six patients who had received a median of 5 cycles (range 1–9) were evaluable for efficacy. The objective tumor response was 16% partial response, 66% stable disease, and 19% progressive disease. The median PFS and OS were 29 months and 47 months, respectively, and were significantly associated with kidney dose, performance status, and Ki 67 levels but not with tumor origin. The overall toxicity was mild, and the most common events were grade 1–2 anemia, thrombocytopenia, fatigue, nausea, and diarrhea. Grade 3–4 toxicity occurred in < 10% of patients and was mostly hematological, with no grade 3–4 renal toxicity. Conclusion: Individualized treatment with 177Lu-DOTATATE based on renal dosimetry is clearly feasible with low toxicity and promising efficacy, showing the potential to further improve outcome beyond the standard approach, and should be further assessed in randomized trials. Trial registration: EudraCT 2011–000,240-16. NCT01456078. https://clinicaltrials.gov/ct2/show/NCT01456078.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Lu-DOTATATE, Dosimetry, Neuroendocrine tumors, Radionuclide therapy
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
49
issue
11
pages
3830 - 3840
publisher
Springer
external identifiers
  • scopus:85128784401
  • pmid:35451612
ISSN
1619-7070
DOI
10.1007/s00259-022-05786-w
language
English
LU publication?
yes
id
f9ca71f6-acec-41e1-a3d2-1b106bdacca5
date added to LUP
2022-06-03 17:23:16
date last changed
2024-09-21 02:13:25
@article{f9ca71f6-acec-41e1-a3d2-1b106bdacca5,
  abstract     = {{<p>Purpose: Radionuclide therapy with <sup>177</sup>Lu-DOTATATE is well established for patients with advanced somatostatin receptor–positive neuroendocrine tumors with a standard schedule of 7.4 GBq at four occasions. However, this approach does not consider individual variability affecting the tumor radiation dose or dose to organs at risk. Therefore, it is important to assess more personalized strategies. The aim of this phase II trial was to evaluate individualized <sup>177</sup>Lu-DOTATATE for which the number of cycles varied based on renal dosimetry. Methods: Patients were eligible if they had a progressive, somatostatin receptor–positive neuroendocrine tumor with a Ki 67 labeling index &lt; 20%. They received cycles of 7.4 GBq of <sup>177</sup>Lu-DOTATATE at 10 ± 2-week intervals until a predefined radiation dose to the kidneys was reached. The primary endpoint was objective tumor response (RECIST v 1.1). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity (CTCAE v. 4.0). Results: Ninety-six patients who had received a median of 5 cycles (range 1–9) were evaluable for efficacy. The objective tumor response was 16% partial response, 66% stable disease, and 19% progressive disease. The median PFS and OS were 29 months and 47 months, respectively, and were significantly associated with kidney dose, performance status, and Ki 67 levels but not with tumor origin. The overall toxicity was mild, and the most common events were grade 1–2 anemia, thrombocytopenia, fatigue, nausea, and diarrhea. Grade 3–4 toxicity occurred in &lt; 10% of patients and was mostly hematological, with no grade 3–4 renal toxicity. Conclusion: Individualized treatment with <sup>177</sup>Lu-DOTATATE based on renal dosimetry is clearly feasible with low toxicity and promising efficacy, showing the potential to further improve outcome beyond the standard approach, and should be further assessed in randomized trials. Trial registration: EudraCT 2011–000,240-16. NCT01456078. https://clinicaltrials.gov/ct2/show/NCT01456078.</p>}},
  author       = {{Sundlöv, Anna and Gleisner, Katarina Sjögreen and Tennvall, Jan and Ljungberg, Michael and Warfvinge, Carl Fredrik and Holgersson, Kajsa and Hallqvist, Andreas and Bernhardt, Peter and Svensson, Johanna}},
  issn         = {{1619-7070}},
  keywords     = {{Lu-DOTATATE; Dosimetry; Neuroendocrine tumors; Radionuclide therapy}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{3830--3840}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{Phase II trial demonstrates the efficacy and safety of individualized, dosimetry-based <sup>177</sup>Lu-DOTATATE treatment of NET patients}},
  url          = {{http://dx.doi.org/10.1007/s00259-022-05786-w}},
  doi          = {{10.1007/s00259-022-05786-w}},
  volume       = {{49}},
  year         = {{2022}},
}