European Commission Approves Enzalutamide in nmHSPC Subset

Enzalutamide (Xtandi) is now approved in the European Union as monotherapy or in combination with androgen deprivation therapy for patients with high-risk biochemical recurrent non-metastatic hormone-sensitive prostate cancer who are ineligible for salvage radiotherapy, according to a press release from Astellas.¹

This approval by the European Commission is based on results from the phase 3 EMBARK trial (NCT02319837).² The trial assessed enzalutamide plus leuprolide for patients with non-metastatic prostate cancer. Patients who received this combination had a 57.6% lower chance of their cancer spreading or dying vs those given leuprolide alone (HR, 0.42; 95% CI, 0.30-0.61; P <.001). For those given enzalutamide monotherapy, the reduction in this risk was 36.9% (HR, 0.63; 95% CI, 0.46-0.87; P = .005).

In April 2024, the European Association of Urology updated its guidelines for this population. Enzalutamide is now recommended for those with high-risk biochemical recurrent non-metastatic hormone-sensitive prostate cancer with or without androgen deprivation therapy after radiation or surgery. Until this point, the association had not come to a consensus on the standard of care for this population.

"When non-metastatic hormone-sensitive prostate cancer recurs and is allowed to evolve, it could potentially lead to metastasis...With this expanded approval for enzalutamide, clinicians now have an important new option to treat [patients] with non-metastatic hormone-sensitive prostate cancer at high risk of metastasizing, which could become a new standard of care." Antonio Alcaraz, MD, chairman of the Department of Urology at the University Hospital Clinic of Barcelona, said in the press release.¹

Of the 1068 patients enrolled in the EMBARK trial, patients were given 160 mg of enzalutamide plus leuprolide (n = 355), 160 mg of enzalutamide monotherapy (n = 355), or placebo plus leuprolide (n = 358).

The risk of prostate-specific antigen progression was reduced by 93% (HR, 0.07; 95% CI, 0.03-0.14; P <.001) in the combination arm and by 67% (HR, 0.33; 95% CI, 0.23-0.49; P <.001) in the monotherapy arm compared with the placebo arm.

The safety profile was consistent with previously reported results of each agent. Most commonly, fatigue and hot flashes were reported as adverse effects in the combination arm. In the monotherapy arm, fatigue, gynecomastia, and hot flashes were most commonly reported.

"This expanded approval for [enzalutamide] is a vitally important advance for patients with non-metastatic hormone-sensitive prostate cancer with high-risk biochemical recurrence and is a testament to our long and ongoing collaboration with a global network of dedicated clinical trial investigators, patient groups, clinical trial participants and their families. Efficacy and safety results from the EMBARK study demonstrate the potential for [enzalutamide] as a new option for treatment in the early, recurrent hormone-sensitive prostate cancer setting,” said Ahsan Arozullah, MD, MPH, senior vice president and head of Oncology Development at Astellas, said in the press release.¹

In November 2023, the FDA approved enzalutamide plus leuprolide for patients in this population.³ Additionally, in March 2024, the European Medicine Agency’s Committee for Medicinal Products for Human Use gave a positive opinion in favor of enzalutamide with or without androgen deprivation therapy in the same population.⁴

References

1. Astellas' XTANDI™ (Enzalutamide) granted European Commission approval for use in additional recurrent early prostate cancer treatment setting. News release. Astellas. April 23, 2024. Accessed April 24, 2024. https://shorturl.at/AGJV3
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. Pfizer and Astellas’ Xtandi approved by U.S. FDA in earlier prostate cancer setting. News release. Astellas. November 17, 2023. Accessed April 24, 2024. https://tinyurl.com/5h84skuh
4. Astellas receives positive CHMP opinion for XTANDI™ in additional recurrent early prostate cancer treatment setting. News release. Astellas Pharma Inc. March 22, 2024. Accessed April 24, 2024. https://tinyurl.com/48cc9jym