China’s National Medical Products Administration has granted approval to enzalutamide for the treatment of patients with metastatic castration-resistant prostate cancer who are asymptomatic or mildly symptomatic following progression on androgen deprivation therapy in whom chemotherapy is not yet clinically indicated.
Andrew Krivoshik, MD, PhD
China’s National Medical Products Administration has granted approval to enzalutamide (Xtandi) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic following progression on androgen deprivation therapy (ADT) in whom chemotherapy is not yet clinically indicated.1
The approval is partly based on findings from the Asian, international, double-blind, placebo-controlled, phase III Asian PREVAIL trial (9785-CL-0232), in which enzalutamide demonstrated a 62% reduction in the risk of prostate-specific antigen (PSA) progression (HR, 0.38; 95% CI, 0.27-0.52; P <.0001) in asymptomatic or mildly symptomatic patients with progressive metastatic prostate cancer who had disease progression despite receiving ADT.2
The regulatory agency also reviewed a single-dose pharmacokinetic study (NCT02294461) in healthy Chinese volunteers, and results from the phase III PREVAIL trial, which enrolled 1700 patients at sites in the United States, Canada, Europe, Australia, Russia, Israel, Asia, including Japan.3
"Currently the treatment options are limited in China for men with metastatic castration-resistant prostate cancer," Andrew Krivoshik, MD, PhD, senior vice president and global therapeutic area head, Oncology Development, of Astellas, the company that develops enzalutamide with Pfizer, stated in a press release. "The approval of enzalutamide in China brings us one step closer to offering physicians a meaningful treatment option in an area where there is a high medical need."
In the Asian PREVAIL trial, investigators evaluated oral enzalutamide at 160 mg daily versus placebo plus gonadotropin-releasing hormone (GnRH) therapy or after bilateral orchiectomy in patients with asymptomatic or mildly symptomatic progressive mCRPC following ADT. The population comprised Asian patients and included approximately 200 who were Chinese.
Additional data from Asian PREVAIL showed that the median time to PSA progression was 8.31 months in the enzalutamide arm compared with 2.86 months for patients who received placebo. Moreover, enzalutamide also led to a 69% reduction in the risk of radiographic disease progression or death compared with placebo (HR, 0.31; 95% CI, 0.20-0.46; P <.0001). Additionally, enzalutamide showed a statistically significant improvement in overall survival (OS) compared with placebo (HR, 0.33; 95% CI, 0.16-0.67; P = .0015).
Regarding safety, the profile of enzalutamide was generally consistent with prior studies of the androgen receptor inhibitor in patients with mCRPC. The most common adverse events (≥10%) that occurred more frequently, at ≥2% over placebo, in the enzalutamide arm were asthenia/fatigue, decreased appetite, hot flush, arthralgia, dizziness/vertigo, hypertension, headache, and decreased weight.
These efficacy and safety data were found to be consistent with the results of the pivotal international phase III PREVAIL trial in the same patient population. In PREVAIL, the 12-month radiographic progression-free survival rate was 65% in patients treated with enzalutamide compared with 14% among those who received placebo (HR, 0.19; 95% CI, 0.15-0.23; P <.001). Moreover, the benefit with enzalutamide was observed over placebo in the time until the initiation of cytotoxic chemotherapy (HR, 0.35), time to first skeletal-related event (HR, 0.72), a complete or partial soft-tissue response (59% vs 5%), time to PSA progression (HR, 0.17), and rate of decline of ≥50% in PSA (78% vs 3%; P <.001 for all comparisons).
Long-term data from PREVAIL were presented at the 2019 Annual European Association of Urology Congress, in which enzalutamide led to a 2-year OS rate of 71% (95% CI, 68-74) versus 62% (95% CI, 58-65) with placebo.4 At a median follow-up of 69 months, the median OS was 35.5 months with enzalutamide versus 31.4 months with placebo.
"The approval of enzalutamide is an important milestone. Tens of thousands of Chinese patients with metastatic castration-resistant prostate cancer could potentially benefit from the reduced risk of disease progression and death found in the Asian PREVAIL study," Hiroshi Hamaguchi, president of Astellas Greater China Commercial, stated in the press release. "The approval also demonstrates a significant step forward for Astellas, with enzalutamide being the first Astellas oncology treatment approved in China."