ProsTIC/PCF Global Webinar 2023: 225-Actinium-PSMA-617: Data and Perspectives from a Medical Oncologist

The Prostate Cancer Foundation (PCF) hosted the 2023 ProsTIC PCF Global Webinar providing a contemporary overview of novel prostate-specific membrane antigen (PSMA)-targeted alpha emitting agents and new targets for prostate cancer. This session included a presentation by Dr. Megan Crumbaker discussing data and perspectives from a medical oncologist regarding 225-Actinium-PSMA-617.

Dr. Crumbaker started her presentation by highlighting that 225-Actinium-PSMA-617 is an alpha emitter with a half life of 10 days, which has a high energy deposition and shorter path length compared to LuPSMA with the potential to:

  • Overcome radiation resistance in LuPSMA resistant men
  • Improve responses with lower PSMA expression
  • Provide better treatment of micro-metastatic disease

However, with potentially less ability to overcome tumoral heterogeneity.

Retrospective data for 225-Ac-PSMA-617 have been summarized by Ma et al. in a systematic review and meta-analysis (6 studies, 201 patients), suggesting PSA50 response rates of 66% (95% CI 60-73%):1225 ac psma images
Additionally, toxicities summarized in this study include [1]: (i) xerostomia in 77.1% of cases (3% Grade 3), (ii) anemia in 30.3% (7.5% Grade 3), (iii) thrombocytopenia in 14.9% (5.5% Grade 3), and (iv) 3% of patients having grade 3 nephrotoxicity. In 2021, Feuerecker and colleagues reported on the safety and activity of 225-Actinium-PSMA-617 among 26 patients that progressed after Lu-177-PSMA.2 The PSA50 response was 65%, and (A) median PSA-PFS was 3.5 months (95% CI 1.8–11.2), (B) median clinical PFS was 4.1 months (95% CI 3–14.8), and (C) median overall survival was 7.7 months (95% CI 4.5–12.1):over time
Grade 3-4 toxicity included anemia (35%), leucopenia (27%), and thrombocytopenia (19%), with grade 1-3 xerostomia in all patients, leading to cessation of treatment in 23% of patients.

When discussing side effects of radioligand therapy, patients often under-report xerostomia. Undoubtedly, xerostomia sequelae have several aspects that affects quality of life, including anorexia, dysgeusia, pain/discomfort, and dental decay. Xerostomia may be defined as follows:

  1. Symptomatic (ie. dry mouth or thick saliva) without significant dietary alteration; unstimulated saliva flow >0.2 mL/min
  2. Moderate symptoms, oral intake alterations (ie. copious water, other lubricants, diet limited to puree and/or soft, most foods); unstimulated saliva flow 0.1 to 0.2 mL/min
  3. Inability to adequately aliment orally, tube feeds or TPN required; unstimulated saliva flow <0.1 mL/min 

Dr. Crumbaker concluded her presentation discussing data and perspectives from a medical oncologist regarding 225-Actinium-PSMA-617 with the following take home messages:

  • 177-Lu-PSMA-617 (or I&T) is very well tolerated and often maintains and/or improves quality of life, however there are issues with durability of response and resistance
  • We need strong rationale to introduce 225-Ac-PSMA, with its increased toxicity and the same target as LuPSMA. These potential reasons include:
    • Treatment options later in the disease course
    • Patients with lower PSMA expression
    • An option for patients following Lutetium resistance with persistent PSMA avid disease

Presented by: Megan Crumbaker, MBBS, PhD, FRACP, Staff Specialist Medical Oncologist, St. Vincent’s Hospital Sydney, Macquarie University Hospital, Sydney, Australia 

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 ProsTIC PCF Global Webinar held virtually on July 19, 2023.

  1. Ma J, Li L, Liao T, et al. Efficacy and Safety of 225Ac-PSMA-617-Targeted Alpha therapy in Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis. Front Oncol. 2022 Feb 3;12:796657.
  2. Feuerecker B, Tauber R, Knorr K, et al. Activity and Adverse Events of Actinium-225-PSMA-617 in Advanced Metastatic Castration-Resistant Prostate Cancer After Failure of Lutetium-177-PSMA. Eur Urol. 2021 Mar;79(3):343-350.