Systemic radioligand therapy with 177Lu-PSMA I&T in patients with metastatic castration-resistant prostate cancer

Objectives Prostate-specific membrane antigen (PSMA) is a potential therapeutic target in patients with metastatic castration-resistant prostate cancer (mCRPC). To report our initial clinical experience with a beta-emitting 177Lutetium-labelled prostate-specific membrane antigen-ligand (177Lu-PSMA I&T) for systemic radioligand therapy in mCRPC patients.

Methods 22 mCRPC patients who experienced treatment failure with both chemotherapy and novel androgen-receptor targeted therapy were treated 8-weekly with up to 4 cycles of 177Lu-PSMA I&T. All patients were reevaluated with a 68Ga-PSMA PET/CT-scan after each cycle. We report safety data, antitumor response with prostate specific antigen (PSA) declines and radiografic tumor response as well as clinical outcome with changes in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and pain severity.

Results The first 3 patients were treated with a lower activity of 3.7 GBq in their first cycle. Due to a favourable safety profile the activity was increased to 7.4 GBq in 19 subsequent patients who completed a total of 40 cycles. With the higher activity no grade 3/4 toxicities were observed. The main non-hematologic and hematologic grade 1/2 toxicities were dry mouth in 7 (37%), anemia in 6 (32%) and thrombopenia in 5 (25%) patients. The proportion of patients achieving a maximum PSA decline of 蠅 30%, 蠅 50% and 蠅 90% was 56%, 28% and 11%, respectively. Combined assessment of bone and soft tissue metastases showed a complete remission in 5%, stable disease in 63% and progressive disease in 32% of patients. ECOG PS improved or was stable in 74% of patients. Of men with bone pain, 58% achieved complete resolution or reduced pain.

Conclusions Radioligand therapy with 177Lu-PSMA I&T appears to be safe and active in heavily preatreated mCRPC patients. Further prospective, randomized and multicentric evaluation under a phase-III protocol is encouraged.