An 82-Year-Old Man with Metastatic Castration-Resistant Prostate Cancer - Episode 3
Dr Matthew R. Smith reviews initial treatment options for a patient with metastatic castration-resistant prostate cancer (mCRPC).
Matthew R. Smith, MD, PhD: For patients who've received primary androgen deprivation therapy, the standard options as first-line treatment for mCRPC include an androgen receptor pathway inhibitor—drugs like abiraterone acetate or enzalutamide, or docetaxel chemotherapy. There are other approved options including sipuleucel-t. Other agents like radium-223 would typically be used in later lines of therapy. There are approved PARP inhibitors, but those 2 are approved only in specific molecular subsets and in later lines of therapy.
In this case, we have a patient with castration-resistant prostate cancer. He had previously documented metastases by conventional imaging, but interestingly enough, at the time of his progression to CRPC, conventional imaging showed no detectable cancer, and it was really only what remained visible or was visible by PSMA PET, a more sensitive imaging modality. In this case[…]it sort of falls in this gray area of whether he's metastatic or non-metastatic by conventional nomenclature. We certainly know he has distant spread, but it's whether or not it's detectable by conventional imaging. The choice of initial salvage therapy with enzalutamide is very reasonable. He did have a PSA decline, as most patients would, but in this older gentleman with some other medical comorbidities, he did not tolerate therapy well and chose to discontinue treatment because of what he described as profound fatigue and difficulty with ambulation. I certainly would not be enthusiastic about persisting or pursuing continued treatment given those side effects.
He was monitored closely while off treatment for several months, and only when we saw a resolution of those symptoms were we comfortable in retreating him. We made the decision to treat him with darolutamide based on his disease state and prior intolerance of enzalutamide. Darolutamide lacks blood-brain barrier penetration. While there are no head-to-head phase 3 trials between darolutamide and enzalutamide, comparison between the phase 3 studies in non-metastatic CRPC suggests a better tolerability of darolutamide. Further support for that point was made in a French trial (ODENZA) that did a head-to-head comparison looking at patient preference between darolutamide and enzalutamide. In that trial, darolutamide had the edge with more patients preferring darolutamide over enzalutamide.
Thankfully, the patient did tolerate darolutamide well and remains on treatment and his PSA continues to decline on therapy, but we do recognize that mCRPC is not yet an approved indication for darolutamide. This patient kind of falls in this gray area because his PSMA PET was the only basis for visible metastatic disease when we treated him. The other reason that it was reasonable to treat him in this fashion was that he had an intolerance of prior enzalutamide treatment.
Transcript edited for clarity.
Case: A 82-Year-Old Man with Metastatic Castration-Resistant Prostate Cancer