MHRA Approves Darolutamide Plus ADT and Docetaxel for Metastatic HSPC

The United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) has approved darolutamide (Nubeqa) tablets in combination with androgen deprivation therapy (ADT) and docetaxel for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC).¹

The approval was supported by data from the phase 3 ARASENS trial (NCT02799602), which demonstrated a 32.5% reduction in the risk of death for patients treated with darolutamide plus ADT/docetaxel compared with placebo plus ADT/docetaxel (HR, 0.68; 95% CI, 0.57-0.80; P < .001).² The median overall survival (OS) with darolutamide plus ADT/docetaxel was not evaluable (NE; 95% CI, NE-NE) vs 48.9 months (95% CI, 44.4-NE) with ADT/docetaxel alone.

“We are delighted that men with prostate cancer in England will have early access to another innovative treatment option,” Antonio Payano, chief executive officer, Bayer UK and Ireland, stated in a press release. “It’s vital that National Health Service [NHS] patients are able to benefit from the best standard of care and full range of emerging therapies today and in the future. It requires direct and sustained collaboration between government, the NHS and the life sciences sector to properly realize these shared ambitions.”

Previously, darolutamide was made available on the United Kingdom’s NHS for patients with localized prostate cancer. In August 2022, the FDA approved darolutamide tablets in combination with docetaxel for adult patients with mHSPC, based on data from ARASENS.³

The international, randomized, multicenter, double-blind, placebo-controlled ARASENS trial enrolled a total of 1306 patients with mHSPC who were randomly assigned to receive oral darolutamide at 600 mg twice daily in combination intravenous docetaxel at 75 mg/m² every 3 weeks for up to 6 cycles or docetaxel alone. Within 12 weeks prior to randomization, all patients received ADT or underwent orchiectomy.

OS served as the trial’s primary end point. Secondary end points were comprised of time to castration-resistant prostate cancer, time to initiation of subsequent antineoplastic therapy, symptomatic skeletal event-free survival, time to worsening symptoms, and safety.

Additional data showed treatment with darolutamide plus ADT/docetaxel significantly delayed time-to-pain progression (HR 0.79; 95% CI, 0.66-0.95; 1-sided P = .006).

Regarding safety, adverse effects (AEs) were similar in the 2 arms. The incidence of the most common AEs occurring in at least 10% of patients were highest during the overlapping docetaxel treatment period in both groups.

Grade 3 or 4 AEs occurred in 66.1% of patients in the darolutamide group, compared with 63.5% in the placebo group. The most common grade 3/4 AE in each group was neutropenia, occurring in 33.7% and 34.2% of patients in the experimental and control arms, respectively.

References

1. Bayer’s Nubeqa receives MHRA approval to treat metastatic prostate cancer. News release. Bayer. PMLive. November 28, 2022. Accessed November 29, 2022. http://bit.ly/3AT3Pzn
2. Smith MR, Hussain M, Saad F, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386(12):1132-1142. doi:10.1056/NEJMoa2119115
3. FDA approves darolutamide tablets for metastatic hormone-sensitive prostate cancer. News. FDA. August 5, 2022. Accessed November 29, 2022. https://bit.ly/3SqCCLw