Strategic positioning of EZH2 inhibition with enzalutamide in the treatment landscape

Dr. Agarwal asks Dr. Morgans how she would position an EZH2 inhibitor with enzalutamide within the prostate cancer treatment landscape. Dr. Morgans explains that combinations with androgen receptor pathway inhibitors (ARPIs) are generally best deployed early in the treatment algorithm, consistent with how the MEVPRO trials are designed. Many patients arrive in first-line metastatic castration-resistant prostate cancer (mCRPC) after prior abiraterone exposure—the population enrolled in MEVPRO-1.

If mevrometostat plus enzalutamide proves superior to standards such as docetaxel in this setting, and if patient-reported outcomes and safety data support its use, an oral combination would likely be preferred over an intravenous infusion option. She highlights that MEVPRO-2 also addresses an important population: patients reaching mCRPC after ADT alone, with no prior ARPI exposure.

Dr. Morgans contrasts the combination with other available options: it offers an oral regimen rather than a taxane or radioligand therapy, does not carry radiation safety restrictions, and—critically—does not require a specific biomarker like the homologous recombination repair (HRR) mutations needed for PARP inhibitors or PSMA expression needed for radioligand therapy. These features support broad use in early disease states to prolong sensitivity to enzalutamide.

In the next episode, "Communicating with patients and families about investigational EZH2 inhibition," Dr. Agarwal shares his approach to balancing hope and realism in clinical trial conversations.