According to Dr. Hofman, FDA approved theranostic will be prostate-specific membrane antigen (PSMA) for prostate cancer. PSMA is highly over-expressed in prostate cancer and several radioactive small molecules (177Lu-PSMA-617 and 68Ga-PSMA-11) are able to target PSMA. Dr. Hofman then highlighted the phase II LuPSMA trial assessing 177Lu-PSMA-617 at his institution, Peter MacCallum Cancer Centre.1 Between August 2015 and December 2016, 30 patients were identified as eligible for treatment, of which 26 (87%) received at least one line of previous chemotherapy (80% docetaxel and 47% cabazitaxel) and 25 (83%) received prior abiraterone acetate, enzalutamide, or both. There were 17 (57%) patients (95% CI 37-75) that achieved a PSA decline of 50% or more and there were no treatment-related deaths. Clinically meaningful improvements in pain severity and interference scores were recorded at all time-points and 11 (37%) patients experienced a ten-point or more improvement in global health score by the second cycle of treatment.
The TheraP trial is a phase II trial of 177Lu-PSMA-617 versus cabazitaxel in men with metastatic castration-resistant prostate cancer progressing after docetaxel, with initial results presented at the 2020 ASCO virtual annual meeting by Dr. Hofman. The primary endpoint was PSA ≥50% response, of which there was a 29% absolute greater PSA ≥50% reduction for men receiving 177Lu-PSMA-617 compared to those receiving cabazitaxel:
Based on these results, Dr. Hofman concluded that in men with progressive disease following docetaxel, 177Lu-PSMA-617 was more active that cabazitaxel with relatively fewer grade 3-4 adverse events and PSA-progression free survival favoring 177Lu-PSMA-617. As such, 177Lu-PSMA-617 represents a potential new class of effective therapy for men with metastatic castration-resistant prostate cancer.
Currently, there is a library of radionuclides available as summarized in the following table:
Dr. Hofman highlighted that among these agents, several are the most promising, including Actinium-225 (225Ac-PSMA), alpha DOTATATE (212Pb-DOTAMTATE), and fibroblast activation protein (117Lu FAP-2286). To conclude, Dr. Hofman emphasized that there are several ongoing PSMA combination trials, including (i) the PRINCE trial: Lu-PSMA plus pembrolizumab in men with mCRPC, (ii) the LuPARP trial: Lu-PSMA plus olaparib, and (iii) the ENZA-P trial: Lu-PSMA versus Lu-PSMA plus enzalutamide.
Presented by: Michael S. Hofman, FRACP, MBBS, Peter MacCallum Cancer Centre, Melbourne, Australia
Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, Augusta, GA, USA, Twitter: @zklaassen_md, at the ASCO20 Virtual Education Program, #ASCO20, August 8-10, 2020.
- Hofman MS, Violet J, Hicks RJ, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): A single-center, single-arm phase 2 study. Lancet Oncol 2018 Jun;19(6):825-833.
Watch: Radionuclide Targeted Treatment in Progressing Metastatic Prostate Cancer - Michael Hofman