Dr Shore on the Implications of the FDA Approval of Enzalutamide for nmCSPC

Neal Shore, MD, FACS, United States chief medical officer, Surgery and Oncology, GenesisCare USA; medical director, Carolina Urologic Research Center, discusses the implications of the FDA approval of enzalutamide(Xtandi) for patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC), highlighting the key unmet needs that this agent will address in this patient population.

Based on findings from the phase 3 EMBARK trial (NCT02319837), the FDA granted approval to enzalutamide for patients with nmCSPC and biochemical recurrence at high risk for metastasis on November 17, 2023. For years oncologists have employed testosterone suppression through androgen deprivation therapy (ADT) for patients with nmCSPC who have undergone surgery, prostatectomy, radiation, and external beam radiation therapy, Shore begins. Although, historically, oncologists lacked solid level 1 evidence to support the use of ADT monotherapy in this population, it was the established treatment approach, he states.

Now, amidst the array of treatments available for patients with prostate cancer, enhancing the efficacy of ADT with an androgen receptor pathway inhibitor (ARPI) such as enzalutamide emerges as a viable strategy, Shore expands. Particularly in patients at high risk of biochemical recurrence, the combination of ADT and enzalutamide proves superior in preventing disease progression compared with luteinizing hormone-releasing hormone (LHRH) monotherapy. Even ARPI monotherapy outperforms LHRH monotherapy in this patient population regarding its ability to delay disease progression, he elucidates.

Additionally, supplementary data on patient-reported outcomes (PROs) from EMBARK were concurrently presented at the 2023 ESMO Congress and published in the New England Journal of Medicine Evidence. These results revealed that patients treated with enzalutamide plus leuprolide or as monotherapy experienced improvements in sexual function vs those who received leuprolide monotherapy, Shore reports. Examination of various Functional Assessment of Cancer Therapy––Prostate subscales and EORTC Quality of Life Questionnaire–validated outcomes further confirms the overall PRO comparability of enzalutamide, he says. These findings are reassuring when considering combination therapy vs LHRH monotherapy for patients in this population, according to Shore.

The FDA's label expansion of enzalutamide for patients with high-risk biochemically recurrent disease indicates the potential benefits of LHRH plus enzalutamide vs enzalutamide monotherapy. EMBARK investigators are closely monitoring patients for overall survival (OS) and anticipate releasing an OS report in 2025, Shore concludes.