FDA to Quickly Review sNDA for Enzalutamide in nmCSPC With High-Risk BCR


The metastasis-free survival benefit of enzalutamide, and other efficacy and safety data are now under FDA review for the potential approval of the drug for patients with non-metastatic castration-sensitive prostate cancer.

  • With the FDA's priority review for enzalutamide (Xtandi) in non-metastatic castration-sensitive prostate cancer (nmCSPC) with high-risk biochemical recurrence (BCR), the agent may be granted accelerated approval by the agency.1

  • In the phase 3 EMBARK study (NCT02319837), enzalutamide plus androgen deprivation therapy achieved a 58% reduction in the risk of distant metastasis or death in patients with nmCSPC and high-risk BCR.

  • Results from EMBARK will also be submitted to global regulatory authorities for consideration.

The FDA has granted priority review to a supplemental new drug application (sNDA) for enzalutamide for the treatment of patients with nmCSPC with high-risk BCR.1

"The FDA’s acceptance of the sNDA and priority review designation for Xtandi in this indication reinforces the urgent need for therapeutic treatments that delay disease progression for men with nmCSPC with high-risk BCR, Neal Shore, MD, FACS," told Targeted OncologyTM.

The groundwork for this potential indication occurred in the phase 3 EMBARK trial, which assessed the efficacy and safety of enzalutamide combined with androgen deprivation therapy (ADT) or enzalutamide alone vs placebo plus ADT in patients with nmCSPC and high-risk BCR. In the study, both enzalutamide/ADT and enzalutamide monotherapy achieved a statistically significant and clinically meaningful improvement in metastasis-free survival (MFS) vs placebo/ADT, according to interim results.1,2

Prostate cancer cells, 3D illustration. Prostate cancer awareness image | Image Credit: © Dr_Microbe -www.stock.adobe.com

Cells of prostate cancer | Image Credit: © Dr_Microbe -www.stock.adobe.com

Of the 1068 treated in the study, 355 received enzalutamide in combination with the ADT, leuprolide acetate; 358 received placebo with leuprolide acetate; and 355 received enzalutamide monotherapy. At a median follow-up of 60.7 months, enzalutamide/ADT led to a significant reduction in the risk of metastasis or death compared with the placebo combination (HR, 0.42; 95% CI, 0.30-0.61; P < .0001) as did enzalutamide alone vs the placebo combination (HR, 0.63; 95% CI, 0.46-0.87; P = .0049).

Prostate specific antigen (PSA) progression, a secondary end point in the trial, favored the enzalutamide/ADT arm over placebo (HR, 0.07; 95% CI, 0.03-0.14) and the enzalutamide monotherapy arm vs placebo (HR, 0.33; 95% CI, 0.23-0.49). In addition, time to first use of new antineoplastic therapy was also superior with enzalutamide/ADT vs placebo/ADT (HR, 0.36; 95% CI, 0.26-0.49) and with enzalutamide alone vs the placebo combination (HR, 0.36; 95% CI, 0.26-0.49). Lastly, overall survival data were immature at the time of the interim analysis, but there was a trend toward OS improvement with enzalutamide/ADT vs placebo (HR, 0.59; 95% CI, 0.38-0.91; P = .0153) as well as with enzalutamide alone compared with placebo/ADT (HR, 0.78; 95% CI, 0.52-1.17; P = .2304).

"No new safety signals have been observed to date and the safety profile of Xtandi plus leuprolide in men with nmCSPC with high-risk BCR was consistent with the established safety profile in other prostate cancer indications. The most common adverse events in participants treated with Xtandi plus leuprolide were hot flush, fatigue, arthralgia, hypertension and fall and in those treated with Xtandi monotherapy were fatigue, gynecomastia, arthralgia and hot flush," said Shore, the US chief medical officer of surgery and oncology at GenesisCare USA and director, CPI at Carolina Urologic Research Center.

EMBARK is a phase 3, randomized study that is ongoing. Patients included in the study have histologically or cytologically confirmed disease and initially underwent radical prostatectomy or radiotherapy. All patients were required to have a PSA doubling time ≤ 9 months, screening PSA by the central laboratory ≥ 1 ng/mL if they have prior prostatectomy or at least 2 ng/mL above the nadir if they had prior radiotherapy, and serum testosterone ≥ 150 ng/dL.3

With a priority review for the sNDA, enzalutamide for nmCSPC with high-risk BCR may be granted accelerated approval.1

"The FDA's granting of a priority review designation reinforces the need to bring new treatment options for patients with high-risk biochemical recurrent nmCSPC," said Chris Boshoff, MD, PhD, chief oncology research and development officer, executive vice president, Pfizer, in the press release. "We believe the EMBARK data demonstrate the potential of Xtandi, if approved, to help patients earlier in the course of their disease, building on Xtandi's foundation as an existing standard of care in prostate cancer."


1. FDA grants priority review for Xtandi® in non-metastatic castration-sensitive prostate cancer with high-risk biochemical recurrence. News release. August 23, 2023. Accessed August 23, 20233. https://tinyurl.com/yc7xvdak

2. Shore N, de Almeida Luz M, De Giorgi L, et al. LBA02-09 EMBARK: A phase 3 randomized study of enzalutamide or placebo plus leuprolide acetate and enzalutamide monotherapy in high-risk biochemically recurrent prostate cancer. J Urol. 2023;210(1):224-226. doi: 10.1097/JU.0000000000003518.

3. Safety and efficacy study of enzalutamide plus leuprolide in patients with nonmetastatic prostate cancer (EMBARK). ClinicalTrials.gov. Updated August 18, 2023. Accessed August 23, 2023. https://clinicaltrials.gov/study/NCT02319837

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