Lutetium-177 PSMA (LuPSMA) theranostics phase II trial: Efficacy, safety and QoL in patients with castrate-resistant prostate cancer treated with LuPSMA

Abstract

Background: 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. Methods: 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. Results: 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%). Conclusions: 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.