Adding darolutamide to ADT extends rPFS in mHSPC

Topline results from the phase 3 ARANOTE trial (NCT04736199) show that the addition of darolutamide (Nubeqa) to androgen deprivation therapy (ADT) led to a statistically significant improvement in radiographic progression-free survival (rPFS) vs ADT alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC), announced Bayer in a news release.¹

Bayer plans to share the data with the FDA and other global health authorities.

Overall, the trial met its primary end point of rPFS. In terms of safety, data were comparable between both arms in the trial. The safety profile with darolutamide was consistent with previous reports, with no new safety signals observed.

Bayer plans to present data from the ARANOTE trial at a forthcoming medical meeting and share the results with the FDA and other global health authorities regarding submission for an expanded approval. Darolutamide, which was developed in a collaboration between Bayer and Orion, is currently approved in the US for the treatment of patients with non-metastatic castration-resistant prostate cancer at high risk for metastatic disease, and in patients with mHSPC in combination with ADT and docetaxel.

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

In total, the international, double-blind, phase 3 ARANOTE trial enrolled 669 adult patients with mHSPC who were randomly assigned to receive 600 mg darolutamide twice daily plus ADT or to a matched placebo plus ADT.

To be included in the trial, patients needed to have histologically or cytologically confirmed adenocarcinoma of the prostate; metastatic disease; an ECOG performance score of 0, 1, or 2; and adequate bone marrow, liver, and renal function. Additionally, patients needed to have started ADT with or without a first-generation anti-androgen at study entry, but not earlier than 12 weeks prior to randomization.³

The primary end point for the trial is rPFS, as measured from the time of randomization to the first documentation of radiological progressive disease or death from any cause, whichever occurs first. The secondary end points for the trial are overall survival, time to castration-resistant prostate cancer, time to initiation of subsequent anti-cancer therapy, time to prostate-specific antigen (PSA) progression, achieving PSA undetectable rates, time to pain progression, and safety.

Final study completion for the ARANOTE trial is anticipated for September 2025.³

“The results of the ARANOTE trial reconfirm that darolutamide, a compound discovered by Orion scientists, is a viable treatment option for patients with metastatic hormone-sensitive prostate cancer. In these patients, darolutamide has now shown efficacy with and without docetaxel, and thus, pending regulatory approval, can provide choices for the personalized treatment regime. I would like to thank all the patients and the investigators who participated in the ARANOTE trial,” said Outi Vaarala, MD, PhD, senior vice president of innovative medicines and research & development at Orion, in a seperate news release.²

The phase 3 ARANOTE trial is part of a larger clinical development program to evaluate darolutamide across various stages of prostate cancer. This program also includes the phase 3 ARASTEP trial (NCT05794906), which is assessing darolutamide plus ADT vs ADT alone in HSPC at high risk for biochemical recurrence who have no evidence of metastatic disease per conventional imaging and a positive PSMA PET/CT at baseline.

The therapy is also being studied in the phase 3 DASL-HiCaP trial (ANZUP1801; NCT04136353), which is assessing the therapy as an adjuvant treatment for patients with localized prostate cancer at high risk of recurrence. The trial is being led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group.²

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. Bayer. Published online and accessed July 17, 2024. https://www.bayer.com/media/en-us/darolutamide-meets-primary-endpoint-in-phase-iii-aranote-trial-in-men-with-metastatic-hormone-sensitive-prostate-cancer/

2. Inside information: Phase III ARANOTE trial of darolutamide in combination with androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer meets primary endpoint. News release. Orion Oyj. Published online and accessed July 17, 2024. https://www.orion.fi/en/newsroom/all-news/releases/stock-releases/2024/inside-information-phase-iii-aranote-trial-of-darolutamide-in-combination-with-androgen-deprivation-therapy-in-men-with-metastatic-hormone-sensitive-prostate-cancer-meets-primary-endpoint/

3. Darolutamide in addition to ADT versus ADT in metastatic hormone-sensitive prostate cancer (ARANOTE). ClinicalTrials.gov. Last updated July 16, 2024. Accessed July 17, 2024. https://clinicaltrials.gov/study/NCT04736199