FDA OKs Enzalutamide for Nonmetastatic Castration-Sensitive Prostate Cancer
Enzalutamide is the first and only androgen receptor signaling inhibitor approved by the FDA in this intent-to-treat population.
- The FDA has approved enzalutamide (Xtandi) for the treatment of nonmetastatic castration-sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR).1
- Enzalutamide is the first and only androgen receptor signaling inhibitor approved by the FDA in this intent-to-treat (ITT) population.
- The approval follows a supplemental new drug application and expedited development and review programs.
Enzalutamide has been approved for the treatment of patients with nmCSPC with high-risk BCR. With this approval, it becomes the first and only androgen receptor signaling inhibitor that is FDA-approved for this population.1
The regulatory decision is supported by findings from the phase 3 EMBARK trial (NCT02319837) which demonstrated that enzalutamide plus androgen deprivation therapy (ADT), leuprolide, (n = 355) reduced the risk of metastasis or death by 58% vs leuprolide alone (n = 358; HR, 0.42; 95% CI, 0.30-0.61; P <.0001).2,3
At a median follow-up of 60.7 months for the combination of enzalutamide plus ADT and 60.6 months with placebo, the median metastasis-free survival (MFS) was not yet reached (NR; 95% CI, NR-NR) with enzalutamide and NR (95% CI, 85.1-NR) with placebo. At 3 years, the MFS rates in the enzalutamide plus ADT arm and placebo arm were 92.9% and 83.5%, respectively, and the 5-year rates were 87.3% and 71.4%, respectively.
PC-3 human prostate cancer cells: © heitipaves - stock.adobe.com
For the secondary end point of prostate specific antigen (PSA) progression, enzalutamide/ADT was favored over placebo (HR, 0.07; 95% CI, 0.03-0.14), as well as the enzalutamide monotherapy arm vs placebo (HR, 0.33; 95% CI, 0.23-0.49). Time to first use of new antineoplastic therapy was also superior with enzalutamide plus ADT vs placebo/ADT (HR, 0.36; 95% CI, 0.26-0.49) and with enzalutamide alone vs placebo (HR, 0.36; 95% CI, 0.26-0.49).
At the time of the interim analysis, overall survival data were immature, but a trend toward OS improvement was seen with enzalutamide/ADT vs placebo (HR, 0.59; 95% CI, 0.38-0.91; P = .0153) as well as with enzalutamide alone vs placebo/ADT (HR, 0.78; 95% CI, 0.52-1.17; P = .2304).
"For patients who were previously treated for prostate cancer and had achieved remission, only to later receive the distressing news of disease recurrence with a risk of metastasis, the emotional toll can be profound," said Courtney Bugler, president and chief executive officer of ZERO Prostate Cancer, in a press release.1 "This approval of XTANDI is a promising treatment option for the community, offering a ray of hope to patients and their caregivers during these challenging times."
About EMBARK
EMBARK was an international, randomized, phase 3 trial which included adult patients with prostate cancer with biochemical recurrence after local therapy who had histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation, signet-cell features, or small-cell features at the time of the initial biopsy before primary definitive therapy.2
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, serum testosterone ≥ 150 ng/dL, and an ECOG performance status of 0 or 1.
Patients were randomized 1:1:1 to receive enzalutamide plus leuprolide, placebo plus leuprolide, or enzalutamide monotherapy. The 2 combination arms were double blinded.
Patients received either 160 mg of enzalutamide plus leuprolide (n = 355), 160 mg of enzalutamide monotherapy (n = 355), or placebo plus leuprolide (n = 358).
