Endocrine Abstracts

Aim: To analyze the safety, efficacy and dosimetry of Lu-177 labeled prostate specific membrane antigen (PSMA) ligand 617 in patients with progressive metastatic castration-resistant prostate cancer (mCRPC), in comparison with Lu-177 PSMA I&T.

Methods: Lu-177 PSMA-617 radioligand therapy (PRLT) was performed in 64 mCRPC patients. The median administered activity per treatment was 6 GBq. Ga-68 PSMA PET/CT was used for patient selection and follow-up. Hematological status, renal and hepatic function and serum prostate specific antigen (PSA) levels were documented before and after therapy.

Results: Lu-177 PSMA-617 demonstrated intense accumulation in the metastases. The absorbed tumor dose was 6.3 mGy/MBq (median). Parotid glands received a higher dose (1.0 mGy/MBq) than kidneys (0.65 mGy/MBq). All patients tolerated the therapy well without any acute adverse effects. Mild xerostomia was observed in five patients. G1 hematological toxicity was noticed in 13 patients, G2 in five and G3-4 pancytopenia in two patients. Mild erythrocytopenia was the commonest sequel. Higher-grade toxicity was observed in patients (n=7) having received chemotherapy or Ra-223 treatment before. The severity of pain was significantly reduced in 6/17 (35.3%) symptomatic patients after PRLT. Decrease in PSA was noted in 48/64 (76.9%) patients. Molecular response evaluation (Ga-68 PSMA PET/CT) in 29 patients followed up after at least two cycles revealed complete remission (CR) in three, partial remission (PR) in 12, stable disease (SD) in five and progressive disease (PD) in nine patients. CT exhibited PR in eight, SD in 14, and PD in seven patients. The median overall survival is yet to be reached and progression-free survival was 12.3 months.

Conclusion: Lu-177 PSMA-617 appears to be safe and effective in progressive mCRPC. The kinetics and dosimetry are similar to Lu-177 PSMA-I&T, the first-ever PSMA inhibitor used at our center.