Enzalutamide plus androgen-deprivation therapy (ADT) prolongs overall survival compared with placebo plus ADT among patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) patients and a PSA doubling time of 10 months or less, according to the latest findings from the PROSPER trial reported at the American Society of Clinical Oncology 2020 Virtual Scientific Program and published concurrently in the New England Journal of Medicine.
Median overall survival was significantly longer in the enzalutamide (160 mg once daily) than the placebo group (67.0 vs 56.3 months, respectively), Cora N. Sternberg, MD, of Weill Cornell Medicine in New York, and colleagues reported. Enzalutamide-treated patients had a significant 27% decreased risk of death compared with placebo recipients. As of October 2019, 288 of 933 patients (31%) in the enzalutamide group and 178 of 468 (38%) in the placebo group had died.
Enzalutamide, an oral androgen-receptor inhibitor, plus ADT previously demonstrated a delay in metastasis and maintenance of quality of life compared with placebo plus ADT, but overall survival data were immature (NCT02003924). In this interim analysis, enzalutamide also outperformed placebo in secondary end points. The time to subsequent antineoplastic therapy, time to cytotoxic chemotherapy, and chemotherapy-free survival were longer in the enzalutamide group than in the placebo group.
“In line with recent studies, these results add to the growing body of evidence that androgen-receptor inhibitors not only delay the time to metastasis but also improve overall survival among men with nonmetastatic, castration-resistant prostate cancer,” Dr Sternberg’s team wrote.
No new adverse events (AEs) were identified in this analysis. The most common AEs were fatigue, musculoskeletal events, fracture, hypertension, and falls. Grade 3 or higher AEs occurred less frequently in the enzalutamide than placebo arm (17 vs 20 per 100 patient-years). Cardiovascular events were the most frequent cause of death, although none of the deaths were directly attributed to enzalutamide use.
According to the investigators, most men who died from a cardiovascular event had a clinically significant history of cardiovascular disease.
In an accompanying editorial, Celestia S. Higano, MD, of the University of Washington in Seattle, suggested: “In men with risk factors for cardiovascular disease (such as hypertension, obesity, diabetes, and hyperlipidemia) who do not have a PSA doubling time of 10 months or less, the risk-benefit ratio of treating with enzalutamide should be considered in these asymptomatic men who may have a more indolent course of disease than those with a PSA doubling time of 10 months or less.”
Dr Sternberg’s team and Dr Higano encouraged close monitoring of enzalutamide-treated patients.
Disclosure: This clinical trial was supported by Pfizer and Astellas Pharma, the codevelopers of enzalutamide. Please see the original reference for a full list of authors’ disclosures.
Sternberg CN, Fizazi K, Saad F, et al. for the PROSPER Investigators. Enzalutamide and survival in nonmetastatic castration-resistant prostate cancer [published online May 29, 2020]. N Engl J Med. doi: 10.1056/NEJMoa2003892
Higano CS. Cardiovascular disease and androgen axis-targeted drugs for prostate cancer [published online May 29, 2020]. N Engl J Med. doi: 10.1056/NEJMe2016433