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2022 Michael & Lori Milken – PCF Young Investigator Award

The Clinical and Immune Landscape Changes in Response to Upfront Lutetium PSMA Therapy in Patients with High-Risk Localized Prostate Cancer

Renu Eapen, MBBS, FRACS (Urology)
Peter MacCallum Cancer Center

Mentors: Michael Hofman, MBBS, Declan Murphy, MC BCh BaO, FRCS Urol, FRACS, Paul Neeson, PhD

Description:

  • Lutetium PSMA (LuPSMA) is a new treatment consisting of a radioactive isotope attached to a prostate cancer-targeting molecule, which brings radiation directly to tumors anywhere in the body. LuPSMA was recently FDA-approved for metastatic castration-resistant prostate cancer and extends survival in these patients. The efficacy of LuPSMA in earlier disease states is currently being evaluated in clinical trials.
  • LuPSMA is hypothesized to activate anti-cancer immune responses, by killing tumor cells in a way that alerts the immune system. However, the effects of LuPSMA on tumor immunity, and whether these immune effects contribute to its efficacy, are unclear.
  • A clinical trial, LuTectomy, is underway at the Peter MacCallum Cancer Center to evaluate the efficacy and toxicity of up-front LuPSMA in patients with high-risk localized prostate cancer before undergoing radical prostatectomy.
  • In this project, Dr Renu Eapen will use samples from patients enrolled into the LuTectomy trial to study changes in tumor-immune biology in response to LuPSMA treatment.
  • How and what changes LuPSMA treatment causes in tumor immune cell types and whether the immune system responses to LuPSMA treatment are associated with patient outcomes of the clinical trial will be investigated.
  • If successful, this project will improve understanding of how LuPSMA works on the immune microenvironment of prostate cancer and may potentially change management of high-risk prostate cancer.
  • The LuTectomy data will inform future studies on upfront or early use of LuPSMA therapy alone or in combination with other treatments to improve outcomes and long-term survival in patients with high-risk localized prostate cancer.

What this means for patients: Dr. Eapen and her team are investigating the efficacy and immune mechanisms of action of LuPSMA as a new treatment strategy in patients with high grade prostate cancer. LuPSMA could represent a new treatment option to cure selected patients with localized prostate cancer. The LuTectomy data will be pivotal in designing the next potentially practice-changing clinical trial.