Intermittent Lu-177-PSMA-617 therapy of metastatic castration-resistant prostate cancer in early responders

1271 Purpose: Various treatment regimens have been recommended for radioligand therapy (RLT) with Lu-177-PSMA-617 in metastatic castration-resistant prostate cancer (mCRPC). Extending the time to maximal renal absorbed dose is highly desirable in patients with more favorable tumor biology, and longer life expectancy. Therefore, we assessed the feasibility of intermittent RLT in patients with an early initial response achieving a low tumor burden during the first three treatment cycles. Methods: RLT was discontinued in 15 responding patients with a PSA doubling time ≥3 months, achieving low tumor load after only 2±1 cycles RLT with 6.6±3.8 GBq Lu-177-PSMA-617 per cycle. Treatment was initiated upon progression, consisting of 2±1 more cycles with 6.6±3.8 GBq each. The mean cumulative activity was 29.4±18.4 GBq. Treatment response was evaluated using PSA sampling according to Prostate Cancer Working Group 3 criteria (PCWG3) and 68Ga-PSMA-PET/CT imaging using mPERCIST criteria. Tumor load was identified as low based on miTNM classification, PROMISE. Complete blood count and estimated glomerular filtration rate (eGFR) were measured at baseline, during treatment course and follow-up period. Toxicity was classified using Common Terminology Criteria for Adverse Events (CTCAE v. 5.0). Kaplan-Meier curve method was used for survival analysis. Results: Re-initiation of RLT with Lu-177-PSMA-617 resulted in partial response in 5 patients (33%), stable disease in 3 patients (20%) and progressive disease in 7 (47%). Median progression free survival (PFS) was 10±3 months after initial treatment and 7±2 after re-initiation. The cumulative renal absorbed dose during the treatment period of 18±7 months was 13.3±8.5 Gy. No patient developed significant renal function loss or bone marrow dysfunction (CTC grade III/IV). Conclusions: Intermittent radioligand therapy with Lu-177-PSMA-617 seems not to comprise the outcome of early responders with low PSA doubling time and tumor load. This treatment regime may be worth considering to prolong the time to maximal cumulative renal absorbed dose enabling further treatment cycles in patients with longer life expectancy. Figure: 68Ga-PSMA PET/CT images of a patient undergoing intermittent therapy with 2+2 cycles. PFS from the treatment beginning was 28 months until progression.