Effective Trade-off between Response and Toxicity by Using a Combination of Ac-225 and Lu-177 Labelled PSMA-617 for Progressive End-Stage Metastatic Prostate Cancer

Ziel/Aim:

The alpha emitter Ac-225 labelled with PSMA-617 has revealed encouraging results in end-stage metastatic prostate cancer (PC). However, xerostomia is dose limiting and might necessitate stopping therapy. We studied the efficacy and toxicity of tandem PSMA radioligand therapy (PRLT), concurrently administering both Lu-177 and Ac-225 labelled PSMA-617.

Methodik/Methods:

Tandem PRLT (1 – 3 cycles), concurrently applying 3 – 5 MBq of Ac-225 PSMA-617 and 3.5 – 7.5 GBq Lu-177 PSMA-617 per cycle, was performed in 30 patients with end-stage PC. Ga-68 PSMA PET/CT, patient questionnaires, PSA and other laboratory parameters were evaluated at least 8 weeks after tandem PRLT in 23 patients.

Ergebnisse/Results:

High tumor-specific uptake and biodistribution was noted on post-therapy scans (Lu-177). There was no severe xerostomia and no treatment discontinuation. G3 thrombocytopenia and G2 anemia/leucocytopenia were noted in 2 patients with progressive disease. Otherwise, there was no worsening of counts even in patients with pre-existing anemia or pancytopenia. No nephrotoxicity or any other organ toxicity occurred. Pain decreased in severity with improvement in the global heath status/Karnofsky performance score, particularly significant in 3 patients presenting in a poor general condition. PSA decline was seen in 13 (56.5%) patients, by > 99% in 3 (13%) and by > 50% in 10 (43.5%) patients. Excellent response with nearly complete remission was observed on Ga-68 PSMA PET/CT in 3 patients. Partial remission was noted in 12 (52%) patients, PD in 10 (43.5%), and mixed response (4.5%) in 1 patient. 5 patients died, median overall survival was 35 weeks, and median progression-free survival 21 weeks.

Schlussfolgerungen/Conclusions:

TANDEM-PRLT, concomitantly administering Ac-225 and Lu-177 PSMA-617, seems to be feasible, safe and effective in end-stage metastatic prostate cancer refractory to Lu-177. It might permit dose estimations. The administered radioactivity of Ac-225 can be lowered and the risk of dose-limiting toxicity be minimized. There might be a potential synergistic effect using two radionuclides with different emission characteristics.