Recent Advances in Nuclear Medicine Theranostics for Cancer: New Isotopes and Targets

(UroToday.com) The American Society of Clinical Oncologist's (ASCO) 2020 virtual education program featured a session on recent advances in nuclear medicine theranostics for cancer, including Michael Hofman discussing new isotopes and targets. Dr. Hofman notes that there are several U.S. Food and Drug Administration (FDA) approved theranostic agents, as summarized in the following table:

TheranosticAgents_ASCOVirtual.png

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:

177Lu-PSMA-617VScabazitaxel_ASCOVirtual.png

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:

radionuclides_ASCOVirtual.png

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. 

References:
  1. 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.
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Watch: Radionuclide Targeted Treatment in Progressing Metastatic Prostate Cancer - Michael Hofman
 
 
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