ASCO 2020: Phase 3 PROSPER Trial Results: Enzalutamide Demonstrates Significant Improvement in OS in Patients with nmCRPC

(UroToday.com) Enzalutamide is an FDA approved androgen receptor antagonist used in the treatment of essentially every phase of advanced prostate cancer, from metastatic hormone-sensitive prostate cancer to metastatic and non-metastatic castration-resistant prostate cancer. The approval of enzalutamide for non-metastatic castration-resistant prostate cancer (nmCRPC) was based on PROSPER1, a double-blind, phase III study that randomly assigned patients with nmCRPC and a PSA doubling time of 10 months or less to ADT + placebo or ADT+ enzalutamide 160 mg daily. Initial data showed that enzalutamide led to 71% lower risk of metastasis or death compared with placebo and was FDA approved for nmCRPC In July 2018. This abstract provides the final overall survival analysis for PROSPER.

PROSPERStudyDesign_ASCO2020.png

Summary: Data on 1401 men are presented today. After a median follow up of approximately 4 years, there were 288 deaths in the enzalutamide arm and 178 deaths in the placebo arm. The median overall survival in the enzalutamide arm was 67 months, compared with 56.3 months in the placebo arm.
PROSPERFInalResults_ASCO2020.png

The median duration of treatment on enzalutamide was 33.9 months, compared with 14.2 months with placebo. In terms of toxicity, about half the men receiving enzalutamide reported grade 3 or higher adverse events compared with 27% of men on placebo. The primary adverse events that were numerically higher with enzalutamide over placebo were falls, fatigue, and hypertension.  Of note, 46% of patients experienced fatigue, 18% fracture, 18% falls, and 8% cognitive impairment.

PROSPERAdverseEvents_ASCO2020.png

Long term follow-up of PROSPER shows that enzalutamide continues to improve overall survival with an HR of 0.73.  This trial also provides data that supports metastases free survival as a potential surrogate endpoint for overall survival, a primary endpoint in all trials for men with nmCRPC. This endpoint also proved valid in ARAMIS and SPARTAN. There are three FDA approved therapies for men with nmCRPC, all of which now have demonstrated an improved overall survival (Darolutamide, Apalutamide, Enzalutamide), with different side effect profiles. Reviewing these with patients, along with financial toxicity, may help patients and oncologists with the decision.

Presented by: Cora N. Sternberg, MD, FACP, Clinical Director of the Israel Englander Institute for Precision Medicine, Weill Cornell Medicine, Former Chief of the Department of Medical Oncology at the San Camillo-Forlanini Hospital in Rome, Italy

Written by: Jason Zhu, MD. Medical Oncologist, Division of Genitourinary Cancers, Levine Cancer Institute, Twitter: @TheRealJasonZhu, at the 2020 ASCO Annual Meeting, Virtual Scientific Program #ASCO20, May 29-31, 2020.

Related Content:

Read: Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer
View: The PROSPER Trial: Chemotherapy-Related endpoints in Patients with nmCPRC - Neal Shore 
email news signup