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2022 John Black Charitable Foundation – PCF Young Investigator Award

Mitigating Toxicity of Novel AR-Targeted Therapies in Advanced Prostate Cancer

Ashwin Sachdeva, MBBS, PhD
University of Manchester

Mentors: Noel Clarke, ChM, Nicholas James, PhD, MBBS, Gerhardt Attard, PhD, MBBS

Description:

  • The use of newer, more intense androgen receptor (AR)-targeted therapies, such as abiraterone and enzalutamide, have dramatically improved survival in patients with advanced prostate cancer.
  • However, these treatments can also increase risk of toxicities such as osteoporosis and sarcopenic obesity, contributing to increased risk of falls and fractures, which detrimentally impact quality of life.
  • Metformin is an anti-diabetic drug that is being tested for its impact on survival in combination with ADT, in patients with advanced prostate cancer in the large multi-armed STAMPEDE clinical trial.
  • Dr. Ashwin Sachdeva is investigating whether metformin, which can reduce the risk of metabolic syndrome and bone degeneration, may also mitigate ADT-related toxicities.
  • In this project, Dr. Sachdeva and team will use CT and bone scan imaging data from ~3,000 patients on the STAMPEDE trial undergoing treatment with metformin + standard of care (ADT, +/- radiation therapy to prostate, +/- docetaxel or abiraterone) vs. standard of care alone, to measure changes in tumor burden, adipose tissue, skeletal muscle components, and bone architecture during treatment, to estimate changes in bone health and sarcopenia (loss of skeletal muscle mass and strength).
  • If successful, this project will determine whether metformin can improve bone and/or metabolic health in patients with advanced prostate cancer undergoing ADT, and validate imaging methods as a means to assess bone and metabolic health.

What this means to patients: Hormone therapies are standard life-prolonging treatments for patients with advanced prostate cancer, but are associated with side effects that are detrimental to quality of life, including negative effects on bone and metabolic health. Dr. Sachdeva’s project will determine whether metformin can reduce risk of ADT-associated side effects including bone and metabolic disorders. This will ultimately help to minimize ADT-toxicity and reduce the risk of falls and fractures, which would improve quality of life of patients with advanced prostate cancer.