Dr Vaishampayan on Patient Considerations When Choosing Between FDA-Approved Therapies in nmCRPC

Ulka Nitin Vaishampayan, MBBS, director, the Phase I Program, Rogel Cancer Center, professor, internal medicine, University of Michigan, discusses patient factors to consider when choosing between apalutamide (Erleada), enzalutamide (Xtandi), and darolutamide (Nubeqa) for the treatment of patients with non-metastatic castration resistant prostate cancer (nmCRPC).

There are 3 FDA-approved regimens for the treatment of patients with nmCRPC: apalutamide, enzalutamide, and darolutamide, Vaishampayan begins. These 3 androgen receptor (AR) inhibitors were approved based on the phase 3 SPARTAN, PROSPER, and ARAMIS, trials, respectively. All 3 clinical trials were similarly designed and were placebo controlled, double blinded, randomized trials with a primary end point of metastasis-free survival (MFS), she explains. Additionally, these trials used standard scans for imaging to determine the presence of metastases, Vaishampayan notes. Moreover, Vaishampayan adds that when considering using these therapies, she typically looks for patients with an adequate life expectancy who are healthy enough to tolerate AR inhibitors, keeping in mind any potential long-term comorbidities. A patient with no major competing comorbidities who has a long-term life expectancy is the kind of patient to select for this treatment, she adds.

It is also important to look at rapid doubling time, Vaishampayan expands. A prostate-specific antigen doubling time of 10 months or less was the threshold used in these studies, and patients receiving one of these 3 agents should have that doubling time as well, although other risk characteristics may also be important for patient selection, Vaishampayan says. Patients with small lymph nodes were also eligible for the studiesand should be considered for these therapies, Vaishampayan adds.

All 3 therapies have similar mechanisms of action with AR inhibition, though Vaishampayan says that she slightly leans toward treatment with darolutamide because of preclinical studies demonstrating the drug’s blood–brain barrier penetration. Patients with risk factors, such as seizures or [prior strokes], were allowed onto this agent’s study, whereas those patients were excluded from SPARTAN and PROSPER. However, all 3 agents have similar MFS outcomes, Vaishampayan emphasizes. Notably, further follow-up data have shown an overall survival benefit with darolutamide compared with placebo, Vaishampayan concludes.