News & Perspective

FDA expands approval for enzalutamide to include nmCRPC

8 months ago, OP Editor

Castrate-resistant prostate cancer (CPRC) occurs when the disease reactivates after initial inhibition by androgen deprivation therapy (ADT).1 Enzalutamide has been recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with non-metastatic castrate-resistant prostate cancer (nmCRPC).2 This novel indication expands the treatment portfolio for enzalutamide, which was previously approved solely for metastatic CRPC (mCRPC).3,4 The new indication makes enzalutamide the only FDA-approved oral drug for treatment of both nmCRPC and mCRPC. A phase III clinical trial (PROSPER) investigated the efficacy of enzalutamide in the treatment of nmCRPC and demonstrated positive clinical outcomes.5

Patients who present with nmCRPC and a rapidly rising prostate serum antigen (PSA) levels despite ADT are at high risk for metastasis.5 PROSPER, an international, double-blind, placebo-controlled phase III clinical trial was conducted to study the effects of enzalutamide on patients with nmCRPC.5 A total of 1,401 patients were enrolled in the study, all with PSA doubling time of 10 months or less.5 These patients continued on ADT and were randomized in a 2:1 ratio to receive enzalutamide or placebo.5

The primary endpoint of the study was metastasis-free survival (MFS), defined as the time until radiographic progression or death.5 Enzalutamide treatment resulted in a significant increase of 21.9 months in MFS as compared to placebo (36.6 vs. 14.7 months; HR=0.29; 95% CI: 0.24-0.35; p<0.001).5 This positive clinical finding paves the way for treatment and prevention of metastasis in nmCRPC patients. “A consistent benefit with regards to MFS in favor of enzalutamide treatment was observed in all the prespecified subgroups. There was no decrease in quality of life associated with enzalutamide treatment,” the researchers wrote.5

Positive results were also observed in the secondary endpoints of PROSPER, which included time to PSA progression, time to first use of antineoplastic therapy, and overall survival (OS).5 As compared to placebo, treatment with enzalutamide resulted in a significant delay in median time to PSA progression (37.2 vs. 3.9 months; HR=0.07; 95% CI: 0.05-0.08; p<0.001).5 Furthermore, patients treated with enzalutamide experienced a longer duration until the time to first antineoplastic therapy (39.6 vs. 17.7 months; HR=0.21; 95% CI: 0.17-0.26; p<0.001).5 Median OS was not reached in the study groups; however, the interim analysis demonstrated a 20% lower risk of death with enzalutamide compared to placebo.5

“This approval is an important progress for men with CRPC, who now have [enzalutamide] as a treatment option regardless of whether or not they have detectable metastatic disease,” said Dr. Steve Brenner, the Senior Vice President and Global Therapeutic Area Head of Oncology at Astellas.6

The safety profile of enzalutamide in PROSPER was also consistent with those reported in previous clinical trials involving men with CRPC.5 The most common adverse event (AE) observed in the enzalutamide arm was fatigue (33% vs. 3%), followed by hot flush (13% vs. <1%) and nausea (11% vs. <1%).5

Enzalutamide was previously indicated for the treatment of mCRPC patients after chemotherapy in 2012; and for chemotherapy-naïve mCRPC patients in 2014 based on global phase III studies (AFFIRM and PREVAIL respectively).3,4 Enzalutamide has been the standard of care in the treatment of mCRPC in the last few years, with more than 250,000 men treated worldwide since its initial approval.6 With its new indication, there is hope for the delay of metastasis in CRPC patients, which may in turn lead to longer OS, delayed cancer-related complications and improved quality of life.5,7



  1. Scher HI, Buchanan G, Gerald W, et al. Targeting the androgen receptor: improving outcomes for castration-resistant prostate cancer. Endocr Relat Cancer. 2004;11(3):459-76.
  2. FDA approves enzalutamide for castration-resistant prostate cancer. U.S. Food & Drug Administration. 2018 (Accessed August 27, 2018, at].
  3. Scher HI, Fizazi K, Saad F, et al. Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy. N Engl J Med. 2012;367:1187-97.
  4. Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. N Engl J Med. 2014;371:424-33.
  5. Hussain M, Fizazi K, Saad F, et al. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2018;378:2465-74.
  6. U.S. FDA Approves XTANDI (enzalutamide) for the Treatment of Men with Non-Metastatic Castration-Resistant Prostate Cancer (CRPC). Business Wire. 2018 (Accessed August 27, 2018, at
  7. Xie W, Regan MM, Buyse M, et al. Metastasis-Free Survival Is A Strong Surrogate of Overall Survival in Localized Prostate Cancer. J Clin Oncol. 2017;35(27):3097-3104.


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