LBA-25 RESIST-PC PHASE 2 TRIAL: 177LU-PSMA-617 RADIONUCLIDE THERAPY FOR METASTATIC CASTRATE-RESISTANT PROSTATE CANCER

Abstract

INTRODUCTION AND OBJECTIVES: Introduction: This is an investigator‐initiated open‐label prospective bi‐centric single‐arm phase 2 clinical trial (NCT03042312) of 177Lu‐PSMA‐617 radionuclide therapy in patients with progressive metastatic castrate‐resistant prostate cancer (mCRPC). METHODS: Methods: Patients with progressive mCRPC (biochemical, radiographic or clinical) after > = 1 novel androgen axis drug (NAAD), either chemotherapy (CTX) naive or post‐CTX, with sufficient bone marrow reserve and normal kidney function were eligible. All patients underwent a screening PSMA PET/CT to confirm target expression. Patients received up to 4 cycles of 177Lu‐PSMA‐617 every 8 ±1 weeks and were randomized into 2 treatment activities groups (6.0 or 7.4 GBq). Kidney dosimetry was performed for the first cycle. Efficacy was defined as serum PSA decline of 50% from baseline at 12 weeks and served as primary endpoint. RESULTS: Results: 64 patients (median PSA 75 ng/ml; range 0.5‐2425) were included in the study. 20% were CTX naive while 80% were post‐CTX (1.9 CTX regimens on average, range 1‐4). 45% completed 4 cycles of 177Lu‐PSMA‐617. Androgen deprivation therapy was given concomitantly in 83%, NAAD in 23% and immunotherapy in 6%. PSA decline of >=50% was observed in 23% of patients at 12 weeks and in 38% of patients at any time (best PSA response). The median time to best PSA response was 22 weeks (range 6‐49 weeks). 16% had a PSA decline of >=90% and 59% had any PSA decline (>0%). Mild and transient (CTCAE grade 1‐2) side effects included xerostomia (72%), nausea/vomiting (69%) and bowel movement disorders (45%). CTCAE grade 3 toxicity included nausea/vomiting (6%), anemia (8%), leukopenia (5%), kidney failure (3%), thrombocytopenia (3%), and neutropenia (3%). The mean kidney dose was 2.7 Gy for the first cycle (range 0.9‐5.9) i.e. 0.4 Gy/GBq (range 0.15‐0.9). There was no difference between the efficacy and toxicity for the 6.0 GBq (n=23) and 7.4 GBq (n=41) treatment arms. CONCLUSIONS: Conclusions: 177Lu‐PSMA‐617 radionuclide therapy is well tolerated in patients with progressive mCRPC. PSA declined by >=50% in 38% of patients. The best PSA response rate occurred after 3 cycles. Updated data will be provided at the time of the conference.