The ARANOTE trial is a phase 3 registration trial that was run outside of the United States and included patients metastatic hormone-sensitive prostate cancer and randomised them to receive ADT and darolutamide, versus ADT and placebo with a primary endpoint of radiographic progression free survival. Key secondary endpoints did include overall survival, safety analysis, and certainly patient-reported quality of life.

Importantly, the endpoint was met, that primary endpoint, with ADT plus darolutamide having superior radiographic progression-free survival versus ADT and placebo. The hazard ratio here was 0.54 and this was highly statistically significant. So this study, overall, did demonstrate that ADT and darolutamide prolonged progression free survival as compared to ADT alone.

What was the methodology?

For the quality of life analysis, the methodology was that we longitudinally assessed patient-reported outcomes by survey instruments, including the brief pain instrument, to understand pain severity, that worst pain that the patient experienced, as well as the FACT-P, which is an overall quality of life measure for patients with prostate cancer.

Specific domains within the FACT-P included things like physical functioning, emotional functioning, social functioning, and prostate cancer-specific concerns. All of these were assessed throughout the trial to get a better understanding of what quality of life was like, what pain was like, from the patient’s perspective.

What did you find?

In the quality of life analysis we found that there was a longer time to pain progression with ATD plus darolutamide versus ATD plus placebo, with a hazard ratio of 0.72. We also found that there was a longer time to deterioration of overall quality of life, and this was about 5.1 months with that darolutamide addition to ADT versus ADT alone.

I think, really importantly, this was a clear separation of the curves and was probably driven by certain domains that were helped even more so. These included things like the social domain and the functional domain, so allowing patients to spend more time with their family as well as functioning and doing those things that they normally do including going to work, as well as urinary symptoms from a prostate cancer-specific perspective, which is certainly important from that patient point of view.

What are the clinical implications of these findings?

I think the clinical implications of these findings are multifactorial. One of these is that we saw that the lower the PSA went within this analysis, the better the quality of life was and the longer the quality of life was maintained. That really helps patients understand that if they can get that better disease control, they will have a longer experience of better quality of life.

Additionally we found that this combination of ADT plus darolutamide could be given in a way that both prolongs radiographic progression free survival as was previously reported, but also prolongs the time to pain progression and also prolongs the time until deterioration of overall quality of life. So it really blends that cancer control quality of life maintenance together with a single treatment.

This is particularly important because there has been a previous indication of ADT and darolutamide only in combination with docetaxel, based on the ARASENS trial data. This would be an additional use of darolutamide in the same population of metastatic hormone-sensitive prostate cancer patients, but without that requirement of having chemotherapy. So for patients especially who either don’t want chemotherapy or it may not be fit for them, this may provide another option in their armamentarium for treatment.