Plenary: Next Frontier, Sunday, Afternoon Session
Presentation Authors: Jeremie Calais*, Los angeles, CA, Wolfgang Fendler, Essen, Germany, Matthias Eiber, Munich, Germany, Michael Lassmann, Würzburg, Germany, Magnus Dahlbom, Los angeles, CA, Rouzbeh Esfandiari, Houston, TX, Jeannine Gartmann, Kathleen Nguyen, Pan Thin, Los angeles, CA, Ken Herrmann, Essen, Germany, Johannes Czernin, Los angeles, CA, Ebrahim Delpassand, Houston, TX
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: 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: 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: 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.
Source of Funding: None