2100 - 177Lu-edotreotide Absorbed Dose In Patients with Gastroenteropancreatic Neuroendocrine Tumors: Dosimetry Results from Compete
Presenter(s)
A. I. Iravani1, E. Deshayes2, L. de Mestier3, A. Buck4, A. Kollár5, M. Sathekge6, K. Herrmann7, T. Hope8, Y. Beqqali9, E. Huber10, and L. Kaiser11; 1Department of Radiology, University of Washington/Fred Hutchinson Cancer Center, Seattle, WA, 2Department of Nuclear Medicine, Institut du Cancer de Montpellier Val d'Aurelle, Montpellier University, Montpellier, France, 3Department of Pancreatology and Digestive Oncology, Université Paris-Cité, Hôpital Beaujon (AP-HP), Clichy, France, 4Department of Nuclear Medicine, Universitätsklinikum Würzburg, Würzburg, Germany, 5Department of Medical Oncology, Inselspital Bern, University of Bern, Bern, Switzerland, 6University of Pretoria, Hatfield, South Africa, 7Universitätsklinikum Essen, Essen, Germany, 8University of California at San Francisco, San Francisco, CA, 9ITM Oncologics GmbH, Garching/Munich, Germany, 10TUM School of Engineering and Design, Professorship of Applied Nuclear Technologies, Technical University of Munich; ITM Oncologics GmbH, Munich, Germany, 11Department of Nuclear Medicine, Ludwig-Maximilians-University (LMU) Hospital; ITM Oncologics GmbH, Munich, Germany
Purpose/Objective(s):
In the Phase 3 COMPETE trial, patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) were randomized to receive 177Lu-edotreotide 7.5 ± 0.7 GBq every 3 months (maximum 4 cycles) or everolimus 10 mg daily (NCT03049189). There was a significant treatment benefit for 177Lu-edotreotide over everolimus in terms of progression-free survival (median PFS: 23.9 vs 14.1 months; p=0.02). Patients in substudy A underwent repeated dosimetry after each 177Lu-edotreotide cycle to characterize variability of lesion and healthy organ absorbed dose coefficients (ADC) across cycles.Materials/Methods:
Patients underwent sequential whole-body planar imaging (2D) at 0.5, 6, 24, and 72 to 96 hours post-dose, and abdominal single-photon emission tomography (SPECT, 3D) 24 hours post-dose for cycles 1 to 4. Target lesions were identified per RECIST 1.1 at baseline and included in hybrid (2D/3D) tumor dosimetry only if classified as dosimetry-evaluable (i.e., positive on SPECT and planar imaging without overlap between lesion and other high uptake regions on planar imaging). Kidney and tumor dosimetry were centrally assessed, using OLINDA 1.1. ADC variability was expressed as coefficient of variation (CV).Results:
Among 33 patients in substudy A, repeated dosimetry for healthy organs was available for 17 patients in all 4 cycles (9 female, 8 male; 8 gastroenteric NET, 9 pancreatic NET), while tumor dosimetry was available in 9 patients for cycles 1, 3 and 4 (5 female, 4 male, 6 gastroenteric NET, 3 pancreatic NET). Median kidney ADCs across cycles 1 to 4 ranged between 0.44 to 0.47 Gy/GBq (Table 1), with median intra-patient variability (%CV) of 14% (range: 2-28%). Median tumor ADC (patient level) decreased from 4.1 Gy/GBq (cycle 1) to 1.8 Gy/GBq (cycle 4). The tumor-to-kidney ADC ratios remained favorable across cycles (Table 1). Intra-patient variability for tumor-to-kidney ADC ratios was large (median %CV of 41%), which is expected given that tumor ADC decreases over cycles.Conclusion:
Kidney ADCs remained constant over time with low intra-patient variability, which allows for estimating individual radiation burden based on cycle 1 dosimetry data. The tumor ADC decreased over time, but the tumor-to-kidney ADC ratio remained positive across cycles. Future research will explore the relationship between absorbed dose and treatment response. Table 1: ADC (Gy/GBq) in Kidneys and Tumors ADC: absorbed dose coefficient; %CV: coefficient of variation; NA: not assessed| Parameter Median (Min; Max) | Kidney ADC (n=17) | Tumor ADC (n=9) | Tumor-to-Kidney ADC Ratio (n=9) |
| Cycle 1 | 0.47 (0.23, 0.71) | 4.10 (0.83, 7.03) | 8.87 (1.20, 30.43) |
| Cycle 2 | 0.44 (0.24, 0.61) | NA | NA |
| Cycle 3 | 0.44 (0.31, 0.78) | 2.48 (0.69, 5.71) | 5.02 (1.68, 12.31) |
| Cycle 4 | 0.46 (0.23, 0.82) | 1.80 (0.91, 3.88) | 4.14 (1.87, 9.10) |
| Intra-patient %CV | 14 (2, 28) | 49 (45, 63) | 41 (25, 117) |