Darolutamide Combo Improves Radiological PFS in Metastatic HSPC

In the double-blind, placebo-controlled ARANOTE trial (NCT04736199), investigators assessed the safety and efficacy of darolutamide plus ADT among patients with metastatic HSPC.

Combining darolutamide (Nubeqa) with androgen deprivation therapy (ADT) significantly improved radiological progression-free survival (rPFS) compared with placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer (HSPC), according to a news release on findings from the phase 3 ARANOTE trial (NCT04736199).¹

The significant rPFS improvement in the darolutamide arm reached the trial’s primary end point. Additionally, safety findings were similar between both treatment arms and affirm the toxicity profile of darolutamide as a treatment for those with advanced prostate cancer.

Investigators plan to present further data from the ARANOTE trial at a future scientific meeting. Developers also intend to share their findings with regulatory health authorities across the world to support expanded indications for darolutamide in metastatic HSPC.

“The results of the ARANOTE trial reconfirm that darolutamide, a compound discovered by Orion scientists, is a viable treatment option for patients with metastatic [HSPC],” Outi Vaarala, MD, PhD, senior vice president of Innovative medicines and research & development at Orion, the developer of darolutamide, said in the press release.¹ “In these patients, darolutamide has now shown efficacy with and without docetaxel, and thus, pending regulatory approval, can provide choices for the personalized treatment regimen.”

In the double-blind, placebo-controlled ARANOTE trial, investigators assessed the safety and efficacy of darolutamide plus ADT among patients with metastatic HSPC. Overall, 669 patients were randomly assigned to receive darolutamide at 600 mg twice daily or placebo in combination with investigator’s choice of ADT. Treatment with ADT consisted of luteinizing hormone-releasing hormone (LHRH) agonists or antagonists or orchiectomy.²

The trial’s primary end point was rPFS. Secondary end points included overall survival, time to castration-resistant prostate cancer, time to beginning subsequent anti-cancer therapy, time to prostate-specific antigen (PSA) progression, PSA undetectable rates, time to pain progression, and adverse effects.

Patients 18 years and older with histologically or cytologically confirmed adenocarcinoma of the prostate, metastatic disease, and initiation of ADT with or without first-generation androgens no earlier than 12 weeks prior to randomization were eligible for enrollment on the trial. Having an ECOG performance status of 0 to 2 and adequate bone marrow, liver, and renal function were additional requirements for study entry.

Those who had prior treatment with LHRH agonists or antagonists apart from neoadjuvant or adjuvant therapy or treatment with radiotherapy within 2 weeks before randomization were not eligible for enrollment. Additional exclusion criteria included patients who have had a stroke, myocardial infarction, severe or unstable angina pectoris, coronary or peripheral artery bypass graft, or congestive heart failure; uncontrolled hypertension; a gastrointestinal disorder expected to interfere with absorption of study treatment; or any other prior malignancy within 5 years before randomization.

According to the news release, ARANOTE is one of multiple studies in a clinical development program evaluating darolutamide across different prostate cancer settings. Investigators of the phase 3 ARASTEP trial (NCT05794906) are assessing darolutamide plus ADT compared with ADT alone in those with hormone-sensitive, high-risk biochemical recurrence prostate cancer who have no sign of metastatic disease based on conventional imaging and a positive PSMA PET/CT result.

Additionally, treatment with darolutamide for patients with localized prostate cancer at a very high risk of recurrence is under assessment as part of the phase 3 DASL-HiCaP or ANZUP1801 trial (NCT04136353).

The FDA previously approved oral darolutamide plus docetaxel for patients with metastatic HSPC in August 2022.³ Supporting data for this approval came from the phase 3 ARASENS study (NCT02799602).

References

1. 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. July 17, 2024. Accessed July 17, 2024. https://tinyurl.com/mynp69r
2. Darolutamide in addition to ADT versus ADT in metastatic hormone-sensitive prostate cancer (ARANOTE). ClinicalTrials.gov. Accessed July 17, 2024. https://tinyurl.com/4mbfzvvb
3. FDA approves darolutamide tablets for metastatic hormone-sensitive prostate cancer. News release. FDA. August 5, 2022. Accessed July 17, 2024. https://bit.ly/3bvsKzF