Darolutamide Plus ADT Shows Strong Efficacy and Quality-of-Life Benefits in mHSPC Without Need for Docetaxel

The ARANOTE trial evaluated darolutamide in combination with androgen deprivation therapy (ADT) for patients with metastatic hormone-sensitive prostate cancer (mHSPC), aiming to determine whether the androgen receptor pathway inhibitor could deliver strong efficacy without the need for docetaxel.

In an interview with Pharmacy Times, Pedro Barata, MD, MSc, FACP, discussed key efficacy results, quality-of-life findings, and how these data further establish darolutamide as a well-tolerated, chemotherapy-free treatment option in this setting.

Q: Could you summarize the key efficacy findings from the ARANOTE trial and what the post hoc analyses revealed about outcomes across different age groups in patients with mHSPC?
Pedro Barata, MD, MSc, FACP: Absolutely. ARANOTE is an important study because it explores the role of darolutamide, a newer androgen receptor pathway inhibitor (ARPI), in addition to ADT, in patients with metastatic hormone-sensitive prostate cancer (mHSPC). The primary end point for the trial was radiographic progression-free survival, and there were several important secondary end points such as overall survival, time to pain, and time to subsequent therapies.

The idea was that since darolutamide is established as a standard of care with docetaxel and ADT for these patients, the question became: do we need docetaxel, and what is the activity of darolutamide on top of ADT versus ADT alone? With that in mind, it’s a positive trial. Darolutamide combined with ADT significantly and clinically improved tumor control, delaying time to CRPC (castration-resistant disease) and improving all major endpoints. Patients experienced longer time to progression, longer time to pain development, and longer time to CRPC, all while preserving quality of life.

These data are important because they help us understand the activity of darolutamide in this population without docetaxel, consistent with what was shown previously in the ARASENS trial. This efficacy data also supported approval of the combination of ADT with darolutamide for men with metastatic hormone-sensitive prostate cancer.

Q: How did darolutamide perform in maintaining quality of life compared with standard androgen deprivation therapy (ADT) alone, and were there notable differences in patient-reported outcomes by age?
Barata: Quality of life and patient-reported outcomes are very important in this setting because patients stay on these therapies for years. We want to control cancer, but also allow patients to live their lives with minimal impact. That’s exactly what we see with darolutamide.

Looking at safety—even before discussing quality of life—when comparing darolutamide with placebo, the safety profile is so favorable that in many cases, you can’t tell whether a patient is receiving darolutamide or placebo. In some cases, patients on darolutamide actually report fewer side effects than those on placebo, such as less fatigue, which is remarkable.

As a result, quality of life clearly favors darolutamide. Patients treated with darolutamide report feeling and living better than those who received placebo. Data presented earlier this year confirmed darolutamide’s favorable safety profile and its significant, sustained positive impact on quality of life. Patients can stay on therapy, maintain control of their cancer, and experience minimal side effects—an important achievement given the long-term nature of treatment in this population.