Darolutamide Plus ADT Provides Statistically Significant rPFS Advantage in mHSPC

Christian Rommel, PhD

The addition of darolutamide (Nubeqa) to androgen deprivation therapy (ADT) led to a statistically significant and clinically meaningful improvement in radiological progression-free survival (rPFS) vs placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC), meeting the primary end point of the phase 3 ARANOTE trial (NCT04736199).¹

The safety profile of darolutamide in the trial was consistent with its established profile, and no new adverse effects were reported. A more comprehensive analysis of the study results is expected to be presented at an upcoming medical meeting and discussed with the FDA regarding submission for regulatory approval.

“We are excited to share the positive results from this phase 3 trial. Following potential regulatory approval, physicians will be able to tailor darolutamide treatment plans with or without docetaxel based on individual patient’s needs,” Christian Rommel, PhD, head of Research and Development at Bayer’s Pharmaceuticals Division, stated in a news release.¹ “Today’s results build on the established efficacy and tolerability profile of darolutamide. We are looking forward to future outcomes of our clinical development program investigating the compound across multiple prostate cancer stages and indications.”

Darolutamide is currently indicated by the FDA for use in combination with docetaxel for the treatment of patients with mHSPC as well as for patients with nonmetastatic castration-resistant prostate cancer.²

Prior to the read out of ARANOTE, darolutamide displayed a statistically significant improvement in overall survival (OS) in combination with docetaxel vs placebo plus docetaxel in patients with mHSPC enrolled in the phase 3 ARASENS trial (NCT02799602). Results from the trial demonstrated a 32% reduction in the risk of death with the addition of the AR inhibitor vs docetaxel alone (HR, 0.68; 95% CI, 0.57-0.80; P < .0001). Data from this trial served as the basis for the agent’s present indication in mHSPC.

With these results darolutamide now has positive data from two pivotal phase 3 trials with and without docetaxel in mHSPC.

In ARANOTE, a double-blind, placebo-controlled trial, investigators randomly assigned 669 patients to receive 600 mg of darolutamide by way of 2, 300-mg tablets twice daily with food or matching placebo, plus investigator’s choice of ADT.³

Eligible patients included those with histologically or cytologically confirmed adenocarcinoma of the prostate with evidence of metastatic disease, an ECOG performance status of 0 to 2, and adequate bone marrow, liver, and renal function. In addition, patients had to have started ADT with either a luteinizing hormone-releasing hormone agonist or antagonist or orchiectomy with or without a first-generation anti-androgen no sooner than 12 weeks prior to randomization.

The primary end point of the study is rPFS, defined as the time from the date of random assignment to the date of first documentation of radiological progressive disease or death from any cause. Secondary end points include overall survival, time from randomization to the date of death from any cause, time from randomization to the date of first castration-resistant event, time to initiation of subsequent anti-cancer therapy, time to prostate-specific antigen (PSA) progression, PSA undetectable rates, time to pain progression, and safety.

Darolutamide is also under evaluation in several other trials including the phase 3 ARASTEP trial (NCT05794906), which is evaluating darolutamide plus ADT vs ADT alone in patients who have HSPC and high-risk biochemical recurrence without evidence of metastatic disease by conventional imaging as well as the phase 3 DASL-HiCaP trial (ANZUP1801; NCT04136353), which is evaluating darolutamide as adjuvant therapy for patients with localized prostate cancer who have a very high risk of recurrence.¹

References

1. Bayer announces positive topline results for NUBEQA (darolutamide) from phase III trial in men with metastatic hormone-sensitive prostate cancer (mHSPC). News release. Business Wire. July 17, 2024. Accessed July 17, 2024. https://www.businesswire.com/news/home/20240716341886/en
2. Nubeqa. Prescribing information. Bayer; 2024. Accessed July 17, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212099s002lbl.pdf
3. Darolutamide in addition to ADT versus ADT in metastatic hormone-sensitive prostate cancer (ARANOTE). ClinicalTrials.gov. Updated July 16, 2024. Accessed July 17, 2024. https://clinicaltrials.gov/study/NCT04736199