Safety and Efficacy of ¹⁷⁷Lutetium-PSMA-617 Radioligand Therapy Shortly after Failing ²²³Radium-Dichloride

Bone-seeking ²²³Radium-dichloride (²²³Ra) is an established treatment prolonging survival and reducing morbidity in selected patients with metastatic castration-resistant prostate cancer (mCRPC) with skeletal involvement. Radioligand therapy with ¹⁷⁷Lutetium-PSMA-617 (¹⁷⁷Lu-PSMA-617) has been increasingly implemented in patients with mCRPC failing conventional treatment options. In this study, the safety and efficacy of ¹⁷⁷Lu-PSMA-617 in patients with progressive bone involvement under treatment with ²²³Ra was assessed. Twenty-eight men (median age 73 years, range 63-89 years) with progressive mCRPC, who started ¹⁷⁷Lu-PSMA-617 within 8 weeks after the last ²²³Ra administration, received a median of 4 (IQR 3-6) and a total of 120 cycles of ²²³Ra and a median of 4 (IQR 2-7) cycles ¹⁷⁷Lu-PSMA-617 with a mean treatment activity of 6.5 ± 1.2 GBq per cycle, reaching a mean cumulative activity of 30.7 ± 23.4 GBq. A PSA response (≥50% PSA decline 12 weeks after the first ¹⁷⁷Lu-PSMA-617 cycle) was observed in 18/28 (64.3%) patients and imaging-based partial remission (PR) was observed in 11/28 (39.3%) patients. Median imaging-based progression-free survival (PFS) was 10 (95% CI, 6-14) months and median overall survival (OS) was 18 (95% CI, 14-22) months. Patients with low bone tumor burden (2-20 lesions) had a significantly longer OS (28 vs. 14 months, p < 0.045) compared to patients with a high tumor burden (>20 lesions). Grade ≥ 3 hematological toxicity was observed in six patients after their last treatment cycle with anemia, leukopenia and thrombocytopenia in 5/28 (17.9%), 4/28 (14.3%) and 6/28 (21.4%) patients, respectively. In progressive bone-metastatic mCRPC patients, prompt initiation of ¹⁷⁷Lu-PSMA-617 after failing ²²³Ra is effective with an acceptable toxicity profile.