Enzalutamide combined with leuprolide produces OS benefit in patients with non-Hodgkin lymphoma with biochemical recurrence

Enzalutamide, combined with leuprolide, demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) compared with placebo plus leuprolide in patients with non-metabolic hormone-sensitive prostate cancer (nmHSPC; also known as non-metabolic castration-sensitive prostate cancer [nmCSPC]) who are at high risk for biochemical recurrence at high risk of metastasis, consistent with EMBARK Key secondary endpoint of the Phase 3 trial (NCT02319837).

Top-line results from the EMBARK OS analysis also showed a favorable trend toward improved OS in patients receiving enzalutamide monotherapy compared with placebo plus leuprolide, although this difference was not statistically significant. These data demonstrate that treatment with [enzalutamide] extends life in men with nmHSPC and high-risk biochemical recurrence after initial treatment with prostatectomy, radiation therapy, or both, further validating EMBARK's metastasis-free survival [MFS] data. While men with nmHSPC at high risk for biochemical recurrence now have more treatment options, these results demonstrate clear clinical benefit, including MFS and OS, supporting the initiation of [enzalutamide] into clinical practice for these patients.

EMBARK researchers reported no new safety signals and the safety findings are considered consistent with the previously demonstrated safety profile of enzalutamide. Preliminary analysis of safety data showed that the most common adverse reactions (AEs) in the enzalutamide/leuprolide and placebo/leuprolide groups included fatigue and hot flashes. The most common adverse events in the monotherapy group were hot flashes, gynecomastia, and fatigue.

[Enzalutamide] is the only androgen receptor inhibitor-based treatment regimen to demonstrate survival benefit in metastatic HSPC and nmHSPC, high-risk biochemical recurrence, and castration-resistant prostate cancer, highlighting its significant impact on patients with advanced prostate cancer. These positive results add to strong clinical support for the use of [enzalutamide] and extend clinical confidence, providing evidence for men at high risk of biochemical recurrence that they may live longer when started [enzalutamide] earlier.

In this double-blind, multinational studyIn the EMBARK trial, 1068 patients with nmHSPC at high risk for biochemical recurrence were randomly assigned to receive enzalutamide 160 mg daily plus leuprolide (n=355), placebo plus leuprolide (n=358), or enzalutamide 160 mg alone (n=355). Preliminary analysis data published in October 2023 showed that the study met its primary endpoint of a statistically significant and clinically meaningful improvement in MFS in patients treated with enzalutamide plus leuprolide versus placebo plus leuprolide. Median follow-up was 60.7 months. The 5-year incidence of multiple sclerosis was 87.3% (95% CI, 83.0%-90.6%) in the enzalutamide/leuprolide group, 71.4% (95% CI, 65.7%-76.3%) in the leuprolide/placebo group, and 80.0% (95% CI, 75.0%-84.1%) in the enzalutamide monotherapy group. The MFS outcome of enzalutamide combined with leuprolide was better than that of leuprolide combined with placebo (HR, 0.42; 95% CI, 0.30-0.61; P<0.001). Enzalutamide monotherapy also had better MFS outcomes than leuprolide plus placebo (HR, 0.63; 95% CI, 0.46-0.87; P=0.005).

It is worth noting that, according to EMBARK data, in November 2023, the U.S. Food and Drug Administration approved enzalutamide for the treatment of biochemically relapsed nmCSPC patients with a high risk of metastasis. Since enzalutamide was first approved in 2012, more than 1.5 million men worldwide with advanced prostate cancer have benefited from it. The scope and rigor of the EMBARK trial demonstrates Astellas and Pfizer's long-term commitment to the cancer prostate community.

References:https://www.onclive.com/view/enzalutamide-plus-leuprolide-yields-os-benefit-in-nmhspc-with-biochemical-recurrence