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

Anna Sundlöv, Katarina Sjögreen Gleisner, Jan Tennvall, Michael Ljungberg, Carl Fredrik Warfvinge, Kajsa Holgersson, Andreas Hallqvist, Peter Bernhardt, Johanna Svensson, Anna Sundlöv, Katarina Sjögreen Gleisner, Jan Tennvall, Michael Ljungberg, Carl Fredrik Warfvinge, Kajsa Holgersson, Andreas Hallqvist, Peter Bernhardt, Johanna Svensson

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 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://ichgcp.net/clinical-trials-registry/NCT01456078.

Keywords: 177Lu-DOTATATE; Dosimetry; Neuroendocrine tumors; Radionuclide therapy.

Conflict of interest statement

Anna Sundlöv declares having received speaker honoraria from Novartis, Ipsen, and Sam Nordic, advisory board fees from Advanced Accelerator Applications, and consultancy fees from Spago Nanomedical.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Kaplan–Meier plots of progression-free survival for all (a), by BED (b), baseline ECOG (c), and Ki 67 labeling index (d)
Fig. 2
Fig. 2
Kaplan–Meier plots of overall survival for all patients (a), by BED (b), baseline ECOG (c), and Ki 67 labeling index (d)
Fig. 3
Fig. 3
Percentage change in sum of longest diameters (SLD) in target lesions from baseline to post-baseline nadir grouped by renal BED

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