Progressive metastatic castrate-resistant prostate carcinoma (mCRPC) is a highly lethal condition. Lutetium-177 (177Lu)-PSMA617, a radiolabelled small molecule, binds with high affinity to prostate specific membrane antigen (PSMA) enabling beta particle therapy targeted to mCRPC.
In this phase II prospective trial, 30 pts with PSMA-avid mCRPC who had failed standard therapies received up to 4 cycles of 177Lu-PSMA617 every 6 weeks. The primary endpoints were PSA and imaging response (PCWG2) and toxicity (CTCAE v4). Other endpoints were quality of life (EORTC QLQ-C30/BM22, BPI), dosimetry, PFS and OS.
All patients were enrolled between 10/2015 and 12/2016 (median age 69 yr, ECOG 1; PSA doubling time 2.2 months) with 3 pts awaiting a final treatment cycle. 87% received prior chemotherapy, 47% cabazitaxel and 83% prior abiraterone and/or enzalutamide. Mean dose was 7.5 GBq (range 4.4 – 8.7 GBq) prospectively adjusted according tumour burden, renal function and weight. At this interim analysis, 17/30 pt (57%) achieved PSA decline >50%, including 11/30 (37%) with decline >80%. In 17 pt with soft tissue disease, objective response (RECIST PR+CR) occurred in 12 pt (71%). Most common adverse events were grade 1 xerostomia (19 pt, 63%) and nausea (15 pt, 50%). Grade 3 or higher hematoxicity occurred in 5 pt (17%); all had baseline thrombocytopenia and were reversible. Following the first cycle of LuPSMA, global health score improved significantly (≥10 points) in 11/30 pt (37%), while in those with bone pain, mean severity score improved significantly (≥ 10 points) in 9/21 pt (43%).
The LuPSMA Phase II trial provides evidence of high response rates and low toxicity with improved QoL and pain reduction in men with mCRPC who have failed conventional therapies.
Clinical trial identification
Australian New Zealand Clinical Trials Registry: ACTRN12615000912583. Universal Trial Number (UTN): U1111-1172-4095.
Legal entity responsible for the study
Peter MacCallum Cancer Centre, Melbourne, Australia
Investigator-initiated trial. Lutetium-177 (no carrier added) supplied by Australian National Nuclear Research and Development Organisation (ANSTO). PSMA617 supplied by Advanced Biochemical Compounds (ABX).
All authors have declared no conflicts of interest.