The first radionuclide based approach used a monoclonal anti-PSMA antibody – J591. It binds extracellular domain with 1-nM affinity. Importantly there are reversible hematological toxicities with grade 4 thrombocytopenia in 47% of patients and myelosuppression is a concern.
Antibody based radionuclide therapy is limited by a slow diffusion into solid tumors and hematoxicity resulting from long circulating time. Therefore, most studies today are focusing on the small molecule PSMA ligands, such as the LU-PMA-617. Preliminary results have shown a significant PSA response after 1 cycle of treatment with this (8 weeks post treatment), with a much greater response after 3 cycles of treatment. Additionally, imaging has shown a major response as well in most patients with more than 50% decrease in disease burden. Actinium- 225 is another PSMA ligand which is rare and expensive, but is an alpha emitter and not a betta emitter, which is now being studied.
As mentioned before, there is concern for hematologic toxicity with white blood cells and platelets requiring to be monitored throughout the entire treatment. Additional adverse effects include mild fatigue and xerostomia.
Dr. Fleshner concluded his excellent presentation by presenting the Lutetium – PSMA-617 clinical trial proposal in Princess Margaret Cancer Center in Toronto, Canada. This trial will randomize metastatic hormone naïve patients to either continued androgen deprivation therapy (ADT), or Lu-PSMA 3 cycles and continued ADT, at a rate of 2:1, respectively. Imaging will be performed every 4 months.
In summary, this is a new class of drugs based on medical isotopes that are changing how we treat PC patients. These agents are currently available in Europe, but not Canada. To date, there have been “miraculous” case reports but there is lack of rigorous data. Hopefully, this can change with the completion of the prospective randomized trial in Toronto, Canada.
Presented By: Neil Fleshner, MD, MPH, FRCSC, Princess Margaret Cancer Center, Toronto, Ontario
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre Twitter: @GoldbergHanan at the 72nd Canadian Urological Association Annual Meeting - June 24 - 27, 2017 - Toronto, Ontario, Canada