Over half of the patients with progressive metastatic castrate-resistant prostate carcinoma (mCRPC) who progressed after standard therapies, achieved a greater than 50% reduction in prostate specific antigen (PSA) levels after receiving 177Lu-PSMA617, according to findings presented at ESMO 2017, the Annual Congress of the European Society for Medical Oncology in Madrid, Spain. After receiving the first dose, many patients reported significantly improved quality of life (QoL) including relief of bone pain.
177Lu-PSMA617 is a radiotherapeutic under evaluation in mCRPC consisting of a Lutetium-177 radiolabelled small molecule that binds with high affinity to prostate specific membrane antigen (PSMA) enabling beta particle therapy that specifically targets mCRPC.
Associate Professor Michael Hofman of the University of Melbourne, Peter MacCallum Cancer Centre, headed a team of researchers in conducting this phase II prospective trial wherein 177Lu-PSMA617 was administered every 6 weeks for up to 4 cycles to 30 enrolled patients with PSMA-avid mCRPC who progressed after standard therapies. 177Lu-PSMA617 was manufactured in the hospital radiopharmacy and patients received a mean dose of 7.5 GBq.
PSA levels significantly reduced
The primary endpoints of the study were the decrease in prostate specific antigen (PSA) according to Prostate Cancer Working Group 2 (PCWG2) criteria and toxicity by common terminology criteria for adverse events (CTCAE) v4. Other endpoints were QoL as measured on the EORTC QLQ-C30, the Bone Pain Inventory (BPI) questionnaires relating to bone pain, dosimetry, progression-free survival (PFS) and overall survival (OS).
The patients were enrolled between October 2015 and December 2016 and had a median age of 69 years. Overall, 87% of patients had received prior chemotherapy and 47% had progressed after second-line cabazitaxel chemotherapy. 83% of patients had received prior abiraterone and/or enzalutamide. Only patients with high uptake on PSMA PET were eligible for treatment.
High response rates achieved with 177Lu-PSMA617
The primary endpoint of a PSA decrease greater than 50% was achieved in 17 (57%) of 30 patients. Remarkably, 12 (40%) patients showed a deep response with PSA decrease of >80%.
Primary endpoint.
© Michael Hofman.
The PFS and OS data have not yet matured and will be presented at the final data analysis.
The most commonly reported adverse events (AEs) included grade 1 xerostomia in 19 (63%) of patients and nausea in 15 (50%) patients. Grade 3 or higher hematoxicity that was attributable to LuPSMA occurred in 5 (17%) patients.
The QoL, as measured using the global health scale showed scores improved significantly directly after the first cycle of LuPSMA. Eleven (37%) patients showed improvement in global health scores of ≥10 points. Nine of 12 (43%) patients experiencing bone pain, showed a significant improvement in mean severity scores improved significantly of ≥ 10 points.
Conclusions
The investigators noted that 177Lu-PSMA617 shows promise as a treatment for mCRPC, which is a highly lethal condition. They concluded that this phase II trial of 177Lu-PSMA617 provided evidence of high response rates and low toxicity in concert with improved QoL and pain reduction in men with mCRPC who have failed conventional therapies.
Over half of patients with progressive metastatic castrate-resistant prostate carcinoma (mCRPC) who progressed after standard therapies, achieved a greater than 50% reduction in PSA levels after receiving 177Lu-PSMA617. After receiving the first dose, many patients reported significantly improved quality of life including relief of bone pain. (785O – Hofman MS, et al.)
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