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More patients with metastatic castration-sensitive prostate cancer (mCSPC) achieved a prostate-specific antigen (PSA) response with apalutamide compared with enzalutamide, researchers reported.

Benjamin Lowentritt, MD, of Chesapeake Urology in Towson, Maryland and colleagues analyzed the electronic medical records of 186 patients treated with apalutamide and 165 treated with enzalutamide. At 6 months, a greater proportion of patients on apalutamide achieved a 90% or greater decline in PSA relative to baseline (PSA90) compared with enzalutamide (69.3% vs 55.6%, P=0.014).

The analysis, presented at the , controlled for age, race, use of androgen-deprivation therapy (ADT), Gleason score, and other potentially confounding factors. "This result continued to remain significant at 9 months and at the end of the follow-up," the researchers wrote in the abstract.

Furthermore, patients on apalutamide achieved a lower PSA more quickly, the study found. The median time to PSA90 was 3.1 months for these patients versus 5.2 months for those receiving enzalutamide. "This real-world study of mCSPC cohorts demonstrates that initiation of apalutamide leads to significantly more patients achieving a deep PSA response more rapidly than patients initiating enzalutamide," the team concluded.

In the following interview, Lowentritt elaborated on the findings and discussed the implications.

Why did you decide to undertake this study, and why did you choose PSA90 as the main outcome?

Lowentritt: Early indicators of treatment response are important to clinicians, particularly those that may predict long-term outcomes for patients. In advanced prostate cancer, several post-hoc analyses of Phase III clinical trials have consistently demonstrated that rapid lowering of PSA, as assessed by measures like PSA90, is associated with better long-term outcomes such as progression-free survival, metastasis-free survival, and overall survival in metastatic, castration-sensitive and non-metastatic, castration-resistant prostate cancer.

PSA90 was specifically selected in our study because deeper PSA reductions have also been more strongly associated with greater long-term benefits than measures like PSA50.

What did the results add to what is already known?

Lowentritt: These results add to the growing body of clinical trial and real-world evidence substantiating the efficacy of next-generation androgen receptor inhibitors for treatment of mCSPC. Without controlled comparative studies physicians are not able to understand if differences in clinical outcomes exist with different next-generation androgen receptor agents for patients with advanced prostate cancers. Real-world data can be used to try to understand these associations.

In this real-world study, it was encouraging to see that apalutamide treatment was associated with more mCSPC patients achieving a PSA90 earlier than with enzalutamide treatment.

Was the PSA90 difference between the two drugs maintained over time?

Lowentritt: In this study, we found that a PSA90 difference favoring apalutamide was detected as early as 3 months and the difference was consistently observed through 12 months and the end of all available follow-up.

How is this data useful to clinicians?

Lowentritt: Despite a large body of evidence that combining next-generation androgen receptor inhibitors with traditional ADT produces better outcomes than use of ADT alone, many patients with mCSPC are still treated with ADT only. It is important to emphasize that patients with advanced prostate cancer require treatment intensification with next-generation androgen receptor inhibitors, and that thoughtful consideration should be given to selecting the best androgen receptor inhibitor to manage an individual patient.

I would like to highlight that, in addition to being a useful clinical marker, PSA response is also an important measure for patients. Many patients anxiously await their latest PSA result and frequently view it as an indication of how their cancer is responding to treatment.

The choice of PSA90 as the primary outcome in this real-world study reflects a growing trend towards the use of more patient-relevant outcomes in clinical research.

Do you plan any additional studies comparing apalutamide and enzalutamide?

Lowentritt: Yes, we hope to continue to evaluate these outcomes associated with apalutamide and other next-generation androgen receptor inhibitors in real-world studies of advanced prostate cancer patients.

Read the study here.