(UroToday.com) In PROSPER (NCT02003924),1 a multinational, double-blind, randomized Phase 3 study that examined enzalutamide (ENZA) in men with nmCRPC continuing androgen deprivation therapy, ENZA significantly improved metastasis-free survival versus placebo (PBO).
In this post hoc analysis, the authors evaluated the association of local radiographic progression (LRP) with deterioration of urinary symptoms and/or genitourinary AEs and ENZA efficacy at the LRP endpoint.
In the study, men with nmCRPC were randomized 2:1 to ENZA (160 mg; n=933) or PBO (n=468). For this study, Odds ratios (ORs) and 95% confidence intervals (CIs) were used to correlate LRP (i.e., progression occurring in soft tissue within the pelvis or death due to any cause within 112 days after treatment discontinuation) with time to deterioration of urinary symptoms, deterioration of prostate cancer symptoms, and/or occurrence of genitourinary AEs. Symptoms were assessed via the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–Prostate Cancer module (urinary subscale) and Functional Assessment of Cancer Therapy–Prostate (prostate cancer subscale). Genitourinary AEs included “Renal and Urinary Disorders” system organ class AEs and preferred terms of urinary tract infection, bacteriuria, and urosepsis.
LRP was delayed by ENZA versus PBO (Table). In both groups, LRP was associated with deterioration of urinary symptoms (ENZA OR [95% CI], 2.11 [1.21, 3.68]; PBO, 1.92 [1.11, 3.33]) and occurrence of genitourinary AEs (ENZA OR [95% CI], 2.38 [1.36, 4.16]; PBO, 2.13 [1.23, 3.68]). Patients on ENZA were less likely to report LRP-associated genitourinary AEs (ENZA, 18.2% [4/22]; PBO, 44.4% [12/27]). ENZA reduced risk of deterioration of symptoms or genitourinary AEs associated with LRP versus PBO (Table). ENZA also reduced time to first symptom or occurrence of genitourinary AE associated with LRP.
Based on this post hoc analysis, the authors conclude that ENZA delays symptomatic local progression, further supporting its utility in the nmCRPC setting. The strong association of local progression with deterioration of urinary symptoms and occurrence of genitourinary AEs may be clinically useful to appropriately address progression-related complications.
Presented by: Marc-Oliver Grimm, MD, Otto-Schott-Institut der Friedrich-Schiller-Universität Jena, Jena, Germany
Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.
- Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF, Ferreira U, Efstathiou E, Madziarska K, Kolinsky MP, Cubero DIG, Noerby B, Zohren F, Lin X, Modelska K, Sugg J, Steinberg J, Hussain M; PROSPER Investigators. Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2197-2206. doi: 10.1056/NEJMoa2003892. Epub 2020 May 29. PMID: 32469184.