EU’s CHMP Recommends Enzalutamide Approval in Non-Metastatic HSPC


The positive opinion is supported by findings from the phase 3 EMBARK trial assessing enzalutamide in patients with biochemically recurrent prostate cancer.

Supporting data for the positive opinion came from the phase 3 EMBARK trial (NCT02319837).

Supporting data for the positive opinion came from the phase 3 EMBARK trial (NCT02319837).

The European Medicine Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion in support of approving enzalutamide (Xtandi) with or without androgen deprivation therapy for adult patients with high-risk biochemically recurrent non-metastatic hormone sensitive prostate cancer (HSPC) who are ineligible to receive salvage radiotherapy, according to a press release from Astellas Pharma, the developers of the agent.1

The European Commission will now review the CHMP’s opinion for approving enzalutamide in this population.

Supporting data for the positive opinion came from the phase 3 EMBARK trial (NCT02319837). According to data published in The New England Journal of Medicine, the 5-year metastasis-free survival rate was 87.3% (95% CI, 83.0%-90.6%) in patients who received enzalutamide plus leuprolide, 71.4% (95% CI, 65.7%-76.3%) in those who were treated with leuprolide only, and 80.0% (95% CI, 75.0%-84.1%) in patients who received enzalutamide monotherapy.2 Treatment with enzalutamide/leuprolide reduced the risk of metastasis or death by approximately 58% compared with leuprolide monotherapy (HR, 0.42; 95% CI, 0.30-0.61; P <.001). Additionally, enzalutamide monotherapy yielded an approximately 37% reduction in the risk of death or metastasis compared with leuprolide only (HR, 0.63; 95% CI, 0.46-0.87; P = .005).

Investigators of the EMBARK trial reported no new safety signals. Additionally, there were no significant differences in quality-of-life outcomes between treatment arms.

“[Patients] with [nonmetastatic] HSPC with high-risk biochemical recurrence are very likely to experience disease progression. With approximately 9 out of 10 of these [patients] developing metastatic disease, the need for new and effective treatment options is critical,” Ahsan Arozullah, MD, MPH, senior vice president and head of oncology development at Astellas, said in the press release.1

“Today's positive opinion from the Committee is an important step forward for providing an additional treatment option for these patients and complements the existing efficacy and safety data supporting the use of [enzalutamide] across the prostate cancer disease continuum. We look forward to [enzalutamide] being potentially the first and only androgen receptor signaling inhibitor approved for this patient population in the European Union.”

In the phase 3 EMBARK trial, 1068 patients were randomly assigned 1:1:1 to receive enzalutamide at 160 mg once a day plus leuprolide every 12 weeks (n = 355), placebo plus leuprolide (n = 358), or enzalutamide only (n = 355).

The trial’s primary end point was metastasis-free survival based on blinded independent central review. Secondary end points included patient-reported outcomes and safety.

Patients with high-risk disease, a serum testosterone level of 150 ng per deciliter or higher, and an ECOG performance status of 0 or 1 were eligible for enrollment on the trial.

The European Medicines Agency previously validated a type II variation application for enzalutamide as a treatment for those with nonmetastatic HSPC and high-risk biochemical recurrence in September 2023.3 The application was supported by data from the EMBARK trial.

The FDA approved enzalutamide for patients with nonmetastatic castration-sensitive prostate cancer (CSPC) in November 2023.4 The agency approved the agent based on findings from the EMBARK trial.

“Previously, treatment options for these patients [with biochemical recurrence], especially those who have a high likelihood of developing metastases were limited,” primary trial investigator Neal Shore, MD, FACS, chief medical officer of Strategic Innovation and Pharmacy, GenesisCare USA, director, CPI, Carolina Urologic Research Center, said in a press release at the time of the FDA approval.4 “The FDA approval of [enzalutamide] for patients with CSPC with [biochemical recurrence] at high risk of metastasis represents an important advancement whereby an androgen deprivation signaling inhibitor, enzalutamide, has achieved standard of care discussion for patient-physician decision-making.”


  1. Astellas receives positive CHMP opinion for XTANDI™ in additional recurrent early prostate cancer treatment setting. News release. Astellas Pharma Inc. March 22, 2024. Accessed March 25, 2024.
  2. Freedland SJ, de Almeida Luz M, De Giorgi U, et al. Improved outcomes with enzalutamide in biochemically recurrent prostate cancer. N Engl J Med. 2023;389(16):1453-1465. doi:10.1056/NEJMoa2303974
  3. European Medicines Agency validates type II variation for Astellas' XTANDI® (enzalutamide) for treatment of non-metastatic hormone-sensitive prostate cancer with high-risk biochemical recurrence. News release. Astellas Pharma Inc. September 12, 2023. Accessed March 25, 2024.
  4. Pfizer and Astellas’ Xtandi approved by U.S. FDA in earlier prostate cancer setting. News release. Astellas. November 17, 2023. Accessed March 25, 2024.
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