EU approval sought for darolutamide plus ADT in mHSPC

Bayer has submitted an application to the European Medicines Agency (EMA) seeking approval of darolutamide (Nubeqa) in combination with androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), the company announced in a news release.¹

At 24 months, the rate of radiographic progression-free survival was 70.3% in the darolutamide arm vs 52.1% in the placebo arm.

Bayer is also seeking approval for the combination in the US. Last month, the company announced that they had completed their submission of a supplemental new drug application (sNDA) to the FDA for the same indication.²

Both the EMA application and the US sNDA are supported by data from the pivotal phase 3 ARANOTE trial (NCT04736199), which were recently presented at the 2024 European Society for Medical Oncology Congress in Barcelona, Spain and concurrently published in The Journal of Clinical Oncology.^3,4

Overall, data from the trial showed that darolutamide plus ADT significantly extended radiological progression-free survival (rPFS) compared with placebo plus ADT in patients with mHSPC.

At 24 months, the rate of radiographic progression-free survival was 70.3% in the darolutamide arm vs 52.1% in the placebo arm, translating to a 46% reduction in the risk of radiological progression or death (HR, 0.54; 95% CI, 0.41-0.71; P < .0001). The median rPFS was not reached in the darolutamide arm, compared with 25.0 months in the placebo arm.

According to the authors, all subgroups derived benefit from treatment with darolutamide plus ADT. The HR for high-volume disease was 0.60 (95% CI, 0.44-0.80), and the HR for low-volume disease was 0.30 (0.15-0.60).

Overall survival (OS) results also suggested clinical benefit from darolutamide plus ADT. At 24 months, the OS rate was 79.8% in the darolutamide arm and 75.5% in the placebo arm.

Darolutamide was associated with a trend toward clinical benefit in the secondary end points of time to metastatic castration-resistant prostate cancer (HR, 0.40; 95% CI, 0.32 to 0.51) and time to prostate-specific antigen (PSA) progression (HR, 0.31; 95% CI, 0.23 to 0.41).

Additionally, 62.6% of patients in the darolutamide arm achieved a PSA less than 0.2 ng/mL at any point during the treatment period, compared with 18.5% of patients in the placebo arm.

Time to pain progression (HR, 0.72; 95% CI, 0.54 to 0.96), and time to subsequent systemic anticancer therapy (HR, 0.40; 95% CI, 0.29 to 0.56) were also delayed in the darolutamide arm.

Regarding safety, the combination was well-tolerated across both study arms. The incidence of treatment-emergent adverse events (TEAEs) was similar between the 2 groups, with TEAEs leading to permanent discontinuation of study drug occurring in 6.1% of patients in the darolutamide arm and 9.0% of patients in the placebo/ADT arm.

In total, the global ARANOTE trial included 669 patients who were randomly assigned 2:1 to receive 600 mg darolutamide twice daily plus ADT (n = 446) or to matching placebo plus ADT (n = 223). The median age of participants was 70 years. Among all participants, 31% were Asian and 9.7% were Black.

The primary end point for the trial was rPFS. Secondary end points included OS, time to castration-resistant prostate cancer, time to PSA progression, time to pain progression, time to subsequent systemic anticancer therapy, and safety.

Darolutamide is currently approved in combination with ADT and docetaxel for patients with mHSPC, as well as in combination with ADT for patients with nonmetastatic castration-resistant prostate cancer.

References

1. Orion’s collaboration partner Bayer submits application for third indication of darolutamide in the EU. News release. Bayer. Published online and accessed October 14, 2024. https://www.bayer.com/media/en-us/bayer-submits-application-for-third-indication-of-darolutamide-in-the-eu/

2. Bayer submits application to U.S. FDA for third indication of darolutamide. News release. Bayer. September 26, 2024. Accessed October 14, 2024. https://www.bayer.com/media/en-us/bayer-submits-application-to-us-fda-for-third-indication-of-darolutamide/

3. Saad F, Vjaters E, Shore ND, et al. Efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase III ARANOTE trial. Presented at: 2024 European Society for Medical Oncology Congress. September 13-17, 2024. Barcelona, Spain. Abstract LBA68. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2024_abstracts/LBA68.html.pdf

4. Saad F, Vjaters E, Shore N, et al. Darolutamide in combination with androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer from the phase III ARANOTE trial. 2024 Sep 16:JCO2401798. doi:10.1200/JCO-24-01798