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Neal D. Shore, MD, explains that in the last 10 years, docetaxel, sipuleucel-T, cabazitaxel, abiraterone, and enzalutamide were all approved for use in patients with castration-resistant prostate cancer. Not only do these therapies have different mechanisms of action, but they also have prolonged life, maintained survival, and maintained quality of life. While the question of what’s next may seem greedy, Shore says that there are, in fact, new therapies on the horizon.
Radium-223, a new isotope, showed amelioration of pain, reduction in skeletal-related events, and improvement in overall survival. Radium-223 is a large particle and has a shallow depth of penetration to the cortical bone, which reduces levels of myelosuppression compared to traditional isotopes like strontium and amarium. When myelosuppression is avoided, the opportunity to offer cytotoxic chemotherapies like docetaxel or cabazitaxel remains.
Ipilimumab, a CTLA-4 antibody blocker, releases the checkpoint on immunotherapy and allows T-cells to be more aggressive. Ipilimumab works differently than sipuleucel-T, possibly allowing for the two drugs to be used together. PROSTVAC, another immunotherapy, is administered subcutaneously rather than intravenously and has shown survival benefit greater than eight months.
Shore expresses his excitement about progress in couplet trials with the approved chemotherapy, docetaxel. Custirsen (OGX-011) in combination with docetaxel delayed progression-free survival and was well tolerated in a phase II study. An oral tyrosine kinase inhibitor, tasquinimod, was well tolerated in a phase II trial and will be completing accrual in a phase III trial.
All of these new agents, Shore says, have different mechanisms of action and could show benefit in efficacy and tolerability after phase III trial completion.