Darolutamide Plus ADT Shows Promise in Treating Metastatic Prostate Cancer

Cancer cell division of two prostate cancer cells in the final stage of cell division: ©PRB ARTS - stock.adobe.com

The nonsteroidal antiandrogen darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) led to improvements in radiological progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC), meeting the primary end point of the phase 3 ARANOTE trial (NCT04736199).¹

“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,” said Christian Rommel, PhD, head of research and development at Bayer’s pharmaceuticals division, in a press release. “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.”

Additional data will be presented at an upcoming medical meeting and shared with regulatory agencies, according to Bayer.

Darolutamide’s safety profile was consistent with what has been established previously; no new safety signals were identified.

About the Phase 3 ARANOTE Trial

The phase 3, double-blind, placebo-controlled ARANOTE study has randomized 669 patients globally with mHSPC to receive 600 mg of darolutamide twice daily or matching placebo plus ADT.¹ Along with the study’s primary end point of rPFS, the secondary end points are overall survival (OS), time to castration-resistant prostate cancer, time to initiation of subsequent anticancer therapy, time to prostate-specific antigen (PSA) progression, PSA undetectable rates, time to pain progression, and incidence of adverse events.²

Patients with histologically or cytologically confirmed prostate adenocarcinoma, metastatic disease, an ECOG performance status of 0 to 2, and adequate bone marrow, liver, and renal functions were eligible for enrollment in the study. Further, patients must have started ADT with or without first-generation antiandrogen, but not earlier than 12 weeks prior to randomization.

Those who received second-generation androgen receptor inhibitors including enzalutamide (Xtandi), darolutamide, and apalutmide (Erleada) were not eligible for enrollment in the study. Further, patients could not have received cytochrome P17 enzyme inhibitors including abiraterone acetate (Zytiga), oral ketoconazole, or chemotherapy for prostate cancer.

About Darolutamide in mHSPC

In August 2022, the FDA approved darolutamide plus docetaxelfor the treatment of adult patients with mHSPC.³ This approval was supported by findings from the ARASENS trial (NCT02799602). In the study, 1306 patients were randomized to receive darolutamide 600 mg twice daily or placebo plus 75 mg/m² of docetaxel. Patients also received a gonadotropin-releasing hormone analog or had a bilateral orchiectomy.

The median OS was not reached (NR; 95% CI, NR-NR) in the darolutamide arm vs 48.9 months (95% CI, 44.4-NR) in the placebo arm (HR, 0.68; 95% CI, 0.57-0.80; P <.0001). Moreover, patients in the darolutamide arm experienced a statistically significant delay in time to pain progression (HR, 0.79; 95% CI, 0.66-0.95; 1-side P =.006).

Regarding safety, the most common adverse events with an incidence over 10% were constipation, decreased appetite, rash, hemorrhage, increased weight, and hypertension. These were experienced in both arms, with a ≥2% increase in the darolutamide arm over placebo and docetaxel.

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. July 17, 2024. Accessed July 17, 2024. https://tinyurl.com/4639ejj9

2. 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

3. FDA approves darolutmaide tablets for metastatic hormone-sensitive prostate cancer. News release. FDA. August 5, 2022. Accessed July 17, 2024. https://tinyurl.com/4w7repye