Dr Dreicer on Improving Clinical Trial Design in Prostate Cancer

Robert Dreicer, MD, deputy director and director of solid tumor oncology in the Division of Hematology/Oncology, and professor of medicine and urology at the University of Virginia Cancer Center, discusses the shortcomings of current clinical trials in prostate cancer and what he sees as the biggest area of improvement.

One of the greatest challenges in designing and interpreting clinical trials of therapeutics for patients with metastatic castration-resistant prostate cancer (mCRPC) is the use of the alternative androgen receptor (AR) inhibitor in the control arm, which many clinicians recognize is of little clinical utility, Dreicer begins. In many cases, the control AR inhibitor is not much more effective than placebo, which highlights the need for active control arms in these trials, Dreicer says. Without adequate comparators, clinicians have little context to use tools like the National Comprehensive Cancer Network guidelines to make fully informed treatment decisions for patients, Dreicer adds.

For example, in the phase 3 PROfound trial (NCT02987543), patients with mCRPC who experienced disease progression following treatment with a new hormonal agent such as enzalutamide (Xtandi) or abiraterone acetate (Zytiga) were randomly assigned 2:1 to receive olaparib (Lynparza) or physician’s choice of enzalutamide or abiraterone. In an article published by Wambeke et al in the Journal of Clinical Oncology in 2022 clinicians argued that this control arm was insufficient due to the fact that the physician’s choice of therapy was limited to agents the patients had already experienced disease progression on before the study and just under 20% of patients previously received both enzalutamide and abiraterone. There was also a significant portion of patients in the study who did not receive prior docetaxel.

A major issue in advanced prostate cancer is the relative lack of level 1 evidence, which often hinders clinicians when they try to recommend certain therapies, Dreicer concludes.