May 29, 2020: “Pfizer Inc. and Astellas Pharma Inc. have announced final results from the overall survival (OS) analysis of the Phase 3 PROSPER trial, which evaluated XTANDI® (enzalutamide) plus androgen deprivation therapy (ADT) versus placebo plus ADT in men with non-metastatic castration-resistant prostate cancer (nmCRPC).
In the trial, XTANDI plus ADT reduced the risk of death by 27% (n=1,401; hazard ratio [HR]=0.73; [95% confidence interval [CI]: 0.61-0.89]; p=0.001) compared to placebo plus ADT.
The median OS was 67.0 months (95% CI: 64.0 to not reached) for men who received XTANDI plus ADT compared to 56.3 months (95% CI: 54.4 to 63.0) with placebo plus ADT. OS was a key secondary endpoint of the trial.
These data were simultaneously published online in the New England Journal of Medicine and presented during the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting.
“Overall survival is a critical endpoint in evaluating a prostate cancer medicine,” said Cora N. Sternberg, M.D., F.A.C.P., Clinical Director, Englander Institute for Precision Medicine and Professor of Medicine in Hematology & Oncology, Weill Cornell Medicine and NewYork-Presbyterian.
“These results add to the body of evidence supporting XTANDI’s potential to reduce the risk of death in men with castration-resistant prostate cancer.”
Related News: Enzalutamide Approved by FDA for metastatic castration-sensitive prostate cancer (mCSPC) Treatment
In findings published in the New England Journal of Medicine in 2018, the PROSPER trial met its primary endpoint of metastasis-free survival (MFS), demonstrating a significant reduction in the risk of developing metastasis or death with XTANDI plus ADT compared to ADT alone in men with nmCRPC (HR=0.29 [95% CI: 0.24-0.35]; p<0.001).
MFS was measured as the time from patients entering the trial until their cancer was radiographically detected as having metastasized, or until death, within 112 days of treatment discontinuation.
The safety profile observed in the final OS analysis was consistent with the 2018 primary analysis and the established safety profile of enzalutamide.
The most common adverse reactions irrespective of relationship to study drug that occurred more frequently (≥10%) in XTANDI plus ADT-treated patients in the PROSPER OS analysis were fatigue (37% vs 16%), hypertension (17% vs 6%), asthenia (10% vs 7%), back pain (13% vs 8%), dizziness (12% vs 6%), diarrhea (12% vs 10%), nausea (13% vs 9%), hot flush (14% vs 8%), fall (18% vs 5%), arthralgia (13% vs 8%), constipation (13% vs 8%), hematuria (10% vs 9%), headache (11% vs 5%) and decreased appetite (12% vs 5%).
In this analysis of the PROSPER trial, Grade 3 or higher adverse reactions were reported in 48% of men treated with XTANDI plus ADT and in 27% of men treated with placebo plus ADT.
Non-Metastatic Castration-Resistant Prostate Cancer
Castration-resistant prostate cancer (CRPC) refers to the subset of men whose prostate cancer progresses on androgen deprivation therapy (ADT) despite castrate levels of testosterone (i.e., less than 50 ng/dL).
Non-metastatic CRPC means there is no clinically detectable evidence of cancer spreading to other parts of the body (metastases), and there is a rising prostate-specific antigen (PSA) level.
Many men with non-metastatic CRPC and a rapidly rising PSA level go on to develop metastatic CRPC.
PROSPER Trial
The Phase 3 randomized, double-blind, placebo-controlled, multi-national trial enrolled 1,401 patients with nmCRPC at sites in the United States, Canada, Europe, South America and the Asia-Pacific region.
PROSPER enrolled patients with prostate cancer that had progressed, based on a rising PSA level despite ADT, but who had no symptoms and no prior or present evidence of metastatic disease.
Of the total patients enrolled, 933 patients were treated with XTANDI at a dose of 160 mg taken orally once daily plus ADT and 468 patients were treated with placebo plus ADT.
The primary endpoint of the PROSPER trial, MFS, was measured as the time from patients entering the trial until their cancer was radiographically detected as having metastasized, or until death, within 112 days of treatment discontinuation.
Key secondary endpoints included OS, time to PSA progression and time to first use of antineoplastic therapy.
For more information on the PROSPER trial, go to www.clinicaltrials.gov.
XTANDI® (enzalutamide)
XTANDI (enzalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with castration-resistant prostate cancer (CRPC) and metastatic castration-sensitive prostate cancer (mCSPC).
