ASCO GU 2021: PROSPER Subgroup Analysis by Age and Region: Overall Survival and Safety in Men With Nonmetastatic Castration-Resistant Prostate Cancer Receiving Androgen Deprivation Therapy Plus Enzalutamide

(UroToday.com) There has been a rapid evolution in treatment options for patients with non-metastatic castration-resistant prostate cancer (nmCRPC) since the spring of 2018. Up until the presentation of SPARTAN and PROSPER trials, reporting on the use of apalutamide and enzalutamide in non-metastatic castration-resistant prostate cancer, at GU ASCO in February 2018, there were no specifically approved treatment options for these patients. These agents, as well as darolutamide (on the basis of data from ARAMIS), were subsequently approved on the basis of demonstrated improvements in metastasis-free survival. Subsequently, further follow-up of SPARTAN, PROSPER, and ARAMIS has demonstrated a significant improvement in overall survival as well. In a plenary abstract presentation in the Poster Highlights Session: Prostate Cancer session at the 2021 ASCO GU Cancers Symposium, Dr. De Giorgi and colleagues presented a subgroup analysis of the PROSPER trial examining the effect of age and region on overall survival and safety outcomes.

The methodology of the PROSPER trial has previously been reported and published. In brief, men with nmCRPC, PSA doubling time ≤ 10 months, and PSA ≥ 2 ng/mL at screening were randomized in a 2:1 fashion to enzalutamide 160mg or placebo, in addition to continuing androgen deprivation therapy. 

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Given the primary outcome, as previously reported, of metastasis-free survival, assessment of overall survival was assessed as a key secondary outcome utilizing a group sequential testing procedure with O’Brien-Fleming-type alpha spending function. In this analysis, the authors performed a multivariable analysis assessing both OS and exposure-adjusted adverse events (AEs), including age (≤ 70 yrs and > 70 yrs), geographic region, and other variables.

In this post-hoc analysis, the authors demonstrated that the overall survival benefit associated with the use of enzalutamide in nmCRPC was consistent across age groups and geographic regions. Compared to placebo, enzalutamide reduced the risk of death similarly in patients aged ≥ 70 yrs (hazard ratio [HR] 0.73; 95% CI 0.58-0.9) and those aged < 70 yrs (HR 0.72, 95% CI 0.5-1.04).

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While age and geographic region didn’t appear to significantly affect outcomes, the authors identified 3 factors associated with mortality: Eastern Cooperative Oncology Group (ECOG) performance status (1 vs 0; HR 1.7; 95% CI 1.4-2.1), a log of PSA (HR 1.2; 95% CI 1.1-1.3), and use of subsequent therapy (yes vs no; HR 2.5; 95% CI 2.1-3.1).

As with efficacy outcomes, overall safety did not differ between age groups and across geographic regions.


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The authors, therefore, conclude that the benefit and toxicity of enzalutamide in nmCRPC are similar regardless of age and geographic region.

Presented by: Ugo De Giorgi, Italian Ministry of Health, Scientific Institute of Romagna for the study and treatment of tumors, in Bologna, Italy

Co-Authors: Maha H. A. Hussain, Neal D. Shore, Karim Fizazi, Bertrand Tombal, David F. Penson, Fred Saad, Eleni Efstathiou, Katarzyna Madziarska, Joyce Leta Steinberg, Jennifer Sugg, Xun Lin, Qi Shen, Cora N. Sternberg

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center Twitter @WallisCJD during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021
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