Enzalutamide/Leuprolide Superior to Leuprolide for MFS in nmCSPC

Prostate cancer, bladder cancer, men's health care: © Tom - stock.adobe.com

Enzalutamide (Xtandi) with leuprolide showed promise as a treatment option and was superior in terms of metastasis-free survival (MFS) for patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC) with high-risk biochemical recurrence vs leuprolide alone, according to findings from the phase 3 EMBARK trial (NCT02319837).^1,2

Findings from the phase 3 trial were published in the New England Journal of Medicine and led by investigators at Cedars-Sinai Cancer Center. Among patients treated with the enzalutamide and leuprolide combination, MFS at 5 years was 87.3% (95% CI, 83.0-90.6) vs 71.4% (95% CI, 65.7-76.3) with leuprolide alone, and 80.0% (95% CI, 75.0-84.1) among those treated with monotherapy. Enzalutamide plus leuprolide was superior to leuprolide alone in regard to MFS (HR, 0.42; 95% CI, 0.30-0.61; P <.001).²

Further, enzalutamide monotherapy was also superior to leuprolide alone (HR, 0.63; 95% CI, 0.46-0.87; P =.005). For safety, the safety profile of enzalutamide was consistent with what has been demonstrated in prior clinical studies. No detrimental effects on quality-of-life were observed.

“If these treatments are approved by the [FDA], our results will be practice changing,” said Stephen Freedland, MD, associate director for Training and Education and the Warschaw, Robertson, Law Families Chair in Prostate Cancer at Cedars-Sinai, and lead author of the study, in a press release.¹ “In the study, both of these new options improved metastasis-free survival while preserving quality of life.”

In the randomized study, 1068 patients with prostate cancer were enrolled from 244 sites in 17 countries. Patients were required to have prostate cancer with high-risk biochemical recurrence and a prostate-specific antigen doubling time of 9 months or less.

Patients were required to have histologically or cytologically confirmed adenocarcinoma of the prostate at initial biopsy; no neuroendocrine differentiation, signet cell, or small cell features; and prostate cancer first treated by radical prostatectomy, radiotherapy, or both, with curative intent.³

Once enrolled, patients were randomized in a 1:1:1 fashion. In the combination arm, patients received enzalutamide at a dose of 160 mg daily with leuprolide every 12 weeks (n = 355). In the leuprolide-alone group, patients were given placebo plus leuprolide (n = 358). In the monotherapy group, patients were treated with enzalutamide alone (n = 355).²

In addition to the primary end point of MFS point in the combination and leuprolide-alone arms, as assessed by blinded independent central review, a key secondary end was MFS in the monotherapy group vs leuprolide-alone group. Investigators also assessed the secondary end points of patient-reported outcomes and safety.

Patients were followed for a median of 60.7 months. Investigators found that those in the combination arm had a reduced risk of metastasis or death by 58% vs leuprolide alone. Enzalutamide alone reduced the risk of metastasis or death by 37% vs leuprolide alone.

“Optimizing therapy for patients with aggressive recurrence after their prostate cancer is initially treated has been an unmet need,” said Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer Center and the phase 1 distinguished chair, in a press release.¹ “The results of this trial point the way to two options which the study showed were more effective than current standard of care, giving these patients and their providers the opportunity to choose a potentially improved course of therapy that best meets their needs.”

REFERENCES:

1. Promising new options for treating aggressive prostate cancer. News release. Cedars-Sinai. October 18, 2023. October 20, 2023. https://tinyurl.com/mr3n2bdu

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. Safety and efficacy study of enzalutamide plus leuprolide in patients with nonmetastatic prostate cancer (EMBARK). ClinicalTrials.gov. Updated August 8, 2023. Accessed October 20, 2023. https://tinyurl.com/bddp6yyy