Fred Saad, MD, University of Montreal Hospital Centers, Montreal, Canada, discusses results from the phase 3 ARANOTE trial which assessed the efficacy and tolerability of adding darolutamide to androgen-deprivation therapy (ADT) among patients with metastatic hormone-sensitive prostate cancer. Results demonstrated that the addition of darolutamide reduced the risk of radiographic progression or death, with this benefit observed across all subgroups.

Dr Saad presented these results at the 2024 European Society of Medical Oncology (ESMO) Congress in Barcelona, Spain. 

Transcript:

Hello, I'm Fred Saad, professor and chairman of the Department of Surgery and head of GU oncology at the University of Montreal and I'm here at ESMO 2024 in Barcelona and I'm very happy to present some of the results from the ARANOTE study. 

ARANOTE is a phase 3, randomized, placebo-controlled, international trial that included patients with metastatic hormone-sensitive prostate cancer. Six hundred and sixty-nine patients were randomized 2-to-1 between darolutamide and placebo, obviously with ADT in both arms, with a primary end point of radiographic progression-free survival or death and with multiple secondary end points that include overall survival, but also importantly, time to metastatic [castration-resistant prostate cancer] CRPC, time to pain progression, PSA response, as well as others. 

In summary, the trial met its primary end point with a 46% reduction in the risk of radiographic progression or death (hazard ratio [HR] 0.54; P value < .0001). And when we look at subgroups, all subgroups benefited from the addition of darolutamide to ADT and that included the high volume and low volume patients, patients with de novo or recurrent metastatic disease so, this is very reassuring that every subgroup that we looked at was benefiting. 

Then we looked at secondary end points. Overall survival was still immature, and we did not power the study for overall survival, but we saw a 19% reduction in the risk of death and we're continuing to follow patients. But other important secondary end points, time to metastatic CRPC, which is the lethal form of prostate cancer, was improved by 60% (HR 0.4; confidence interval < 1). We also had a delay in progression of pain by 28% and PSA response was much higher in the darolutamide arm, going above 62% of patients reaching undetectable PSA versus only 18% with ADT alone, and time to PSA progression was also improved by 69% compared to giving ADT alone. 

The important aspect of this trial was also looking at how patients tolerate darolutamide in this setting, and we saw that in terms of adverse events, whether it's all-grade, grade 3/4, was very similar to the placebo arm using darolutamide. In fact, less patients discontinued therapy in the darolutamide arm than in the placebo arm and in terms of [androgen receptor pathway inhibitor] ARPI-related adverse events, fatigue, which is one of the most common complaints, was a little bit less in the darolutamide arm than in the placebo arm. All reassuring points that we're not adding much to the toxicity of ADT alone in patients getting darolutamide in the hormone-sensitive setting. 

We already had survival data from ARASENS in combination with docetaxel and in ARAMIS for non-metastatic CRPC, so we know [darolutamide] is an effective agent and now we hope that this trial will allow patients to be able to get access to darolutamide without requiring docetaxel, for patients who don't need docetaxel or cannot tolerate docetaxel when they have [metastatic hormone sensitive prostate cancer] mHSPC. 

Thank you very much for your attention.
 

Source: 

Saad F, Vjaters E, Shore ND, et al. Efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase III ARANOTE trial. Presented at 2024 ESMO Congress. September 13-17, 2024. Abstract LBA68