Case 2023: Alejandro (expert opinion by E. Castro)

Both abiraterone and enzalutamide have demonstrated improved overall survival (OS) in mCRPC before or after docetaxel. However, germline BRCA2 carriers seem to progress to ARTA more rapidly than non-carriers. Patients with germline BRCA2 mutations have very poor outcomes when conventionally treated with taxanes or ARTA, and their OS has been reported to be half of that of non-carriers. PARPi alone or in combination with ARTA significantly improves their outcomes. At present, we lack information about whether the combination is superior to a PARPi in monotherapy, but considering the poor prognosis of these patients and that PARPi monotherapy is only approved after progression to ARTA, my personal election would be to give Alejandro the combo and to not delay the PARPi. Cabazitaxel has demonstrated to improve OS after progression to docetaxel. Germline BRCA2 mutations do not seem to preclude response to cabazitaxel. However, germline BRCA2 carriers seem to progress to taxanes more rapidly than non-carriers. Radium223 has demonstrated to improve OS in patients with bone disease after progression to docetaxel. However, the drug activity seems to be limited to skeletal disease and this patient already has metastatic lymphadenopathies. Furthermore, the current EMA approval is for patients whose disease has already progressed to ≥2 lines of therapy.

This educational activity is supported by AstraZeneca.