Effects of androgen receptor signaling inhibitors on absorbed doses in mCRPC patients undergoing [<sup>177</sup>Lu]Lu-PSMA-617 or [<sup>177</sup>Lu]Lu-PSMA-I&T therapy: dosimetry results.
ARSi did not significantly enhance tumor absorbed doses in mCRPC patients receiving [177Lu]Lu-PSMA therapies. Larger studies are needed to confirm these findings.
Where it sits
this study against the rest of the vipivotide corpusSummary and findings
This study evaluated the dosimetry effects of androgen receptor signaling inhibitors (ARSi) in combination with [177Lu]Lu-PSMA-617 or [177Lu]Lu-PSMA-I&T radioligand therapy in 50 mCRPC patients. The absorbed doses in tumor lesions and organs-at-risk were compared between a Combination Group and a Control Group. No significant enhancement in tumor absorbed doses was observed with ARSi therapy.
Abstract
<h4>Background</h4>Androgen receptor signaling inhibitors (ARSi) have significantly improved clinical outcomes in men with prostate cancer (PCa). Preliminary data suggest the potential for ARSi to enhance PSMA expression in patients with mCRPC. In this analysis, we present preliminary dosimetry results from mCRPC patients treated with either [<sup>177</sup>Lu]Lu-PSMA-617 or [<sup>177</sup>Lu]Lu-PSMA-I&T radioligand therapy (RLT) in combination with ARSi compared to a Control Group of patients receiving [<sup>177</sup>Lu]Lu-PSMA-617 or [<sup>177</sup>Lu]Lu-PSMA-I&T monotherapy.<h4>Methods</h4>This retrospective analysis was performed at a single center, including 50 patients diagnosed with mCRPC who underwent their first cycle of [<sup>177</sup>Lu]Lu-PSMA-617 (n = 37) or [<sup>177</sup>Lu]Lu-PSMA-I&T (n = 13) RLT ± concomitant ARSi treatment (abiraterone or enzalutamide). Patients were divided into a Combination Group (RLT + ARSi, n = 25) and a Control Group (RLT only, n = 25). Quantitative SPECT imaging was performed at 3 time points: 24 h (+ CT), 48 h, and 72 h post-administration of the initial cycle of RLT. Tumor lesions were segmented using the 24 h SPECT images, while organs-at-risk (kidney, spleen, liver) were delineated on the corresponding CT. Absorbed doses were calculated by applying a mono-exponential curve fit, incorporating local density scaling. Dosimetry results were evaluated separately for each radioligand.<h4>Results</h4>Overall, 148 tumor lesions were included in this analysis (median 3 lesions per patient). The median tumor absorbed dose was comparable between the Combination Group and the Control Group: [<sup>177</sup>Lu]Lu-PSMA-617 (2.1 ± 4.0 Gy/GBq vs 1.5 ± 1.7 Gy/GBq, p = 0.24) and [<sup>177</sup>Lu]Lu-PSMA-I&T (1.2 ± 1.2 Gy/GBq vs 1.2 ± 3.5 Gy/GBq, p = 0.21). Furthermore, the median absorbed dose in organs-at-risk was comparable between the two groups in [<sup>177</sup>Lu]Lu-PSMA-617: Kidneys: 0.28 ± 0.11 Gy/GBq vs 0.27 ± 0.13 Gy/GBq, p = 0.90; Spleen: 0.05 ± 0.05 Gy/GBq vs 0.06 ± 0.05 Gy/GBq, p = 0.75; Liver: 0.08 ± 0.03 Gy/GBq vs 0.07 ± 0.04 Gy/GBq, p = 0.75). A statistically significant difference was noted in kidneys and liver for [<sup>177</sup>Lu]Lu-PSMA-I&T: Kidneys: 0.21 ± 0.10 Gy/GBq vs 0.30 ± 0.08 Gy/GBq, p = 0.01; Spleen: 0.02 ± 0.02 Gy/GBq vs 0.04 ± 0.03 Gy/GBq, p = 0.20; Liver: 0.02 ± 0.01 Gy/GBq vs 0.04 ± 0.01 Gy/GBq, p = 0.01.<h4>Conclusion</h4>In this pilot cohort, concomitant ARSi therapy did not significantly enhance tumor absorbed doses in patients receiving [<sup>177</sup>Lu]Lu-PSMA-617 or [<sup>177</sup>Lu]Lu-PSMA-I&T RLT. Further prospective studies with larger patient numbers are needed to evaluate the impact of concomitant ARSi treatment on the absorbed doses in mCRPC tumor lesions.
Background
The study investigates the potential impact of androgen receptor signaling inhibitors (ARSi) on the dosimetry of radioligand therapies in metastatic castration-resistant prostate cancer (mCRPC) patients. ARSi have previously shown to improve clinical outcomes in prostate cancer, and there is preliminary evidence suggesting they may enhance PSMA expression. This study aims to explore whether ARSi can increase the absorbed dose in tumor lesions when used with [177Lu]Lu-PSMA-617 or [177Lu]Lu-PSMA-I&T therapies.
Methods
This retrospective analysis included 50 mCRPC patients at a single center, divided into a Combination Group (RLT + ARSi, n=25) and a Control Group (RLT only, n=25). Patients received either [177Lu]Lu-PSMA-617 (n=37) or [177Lu]Lu-PSMA-I&T (n=13). Dosimetry was assessed using quantitative SPECT imaging at 24, 48, and 72 hours post-administration. Tumor lesions and organs-at-risk were delineated, and absorbed doses were calculated using a mono-exponential curve fit.
Results
The median tumor absorbed dose was similar between the Combination and Control Groups for both radioligands: [177Lu]Lu-PSMA-617 (2.1 ± 4.0 Gy/GBq vs 1.5 ± 1.7 Gy/GBq, p=0.24) and [177Lu]Lu-PSMA-I&T (1.2 ± 1.2 Gy/GBq vs 1.2 ± 3.5 Gy/GBq, p=0.21). In organs-at-risk, significant differences were observed in kidneys and liver for [177Lu]Lu-PSMA-I&T, but not for [177Lu]Lu-PSMA-617.
Interpretation
The study found no significant enhancement in tumor absorbed doses with the addition of ARSi, suggesting that ARSi may not improve the efficacy of [177Lu]Lu-PSMA-617 or [177Lu]Lu-PSMA-I&T therapies in terms of dosimetry. The statistically significant differences in organ doses for [177Lu]Lu-PSMA-I&T warrant further investigation. The study's limitations, including its small sample size and retrospective design, highlight the need for larger, prospective trials.
Key findings
- 2.1 ± 4.0 Gy/GBq vs 1.5 ± 1.7 Gy/GBq for [177Lu]Lu-PSMA-617, p=0.24
- 1.2 ± 1.2 Gy/GBq vs 1.2 ± 3.5 Gy/GBq for [177Lu]Lu-PSMA-I&T, p=0.21
- Kidneys: 0.28 ± 0.11 Gy/GBq vs 0.27 ± 0.13 Gy/GBq for [177Lu]Lu-PSMA-617, p=0.90
- Kidneys: 0.21 ± 0.10 Gy/GBq vs 0.30 ± 0.08 Gy/GBq for [177Lu]Lu-PSMA-I&T, p=0.01
- Liver: 0.02 ± 0.01 Gy/GBq vs 0.04 ± 0.01 Gy/GBq for [177Lu]Lu-PSMA-I&T, p=0.01
Limitations
- single-center study
- retrospective design
- small sample size (n=50)
- short follow-up period
- preliminary dosimetry results