257O - Association of enzalutamide (ENZA) duration of treatment (DOT) and overall survival (OS) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Post hoc analysis from PREVAIL

Background

In the phase 3 PREVAIL trial (NCT01212991), ENZA significantly reduced risk of death vs placebo (HR, 0.83; 95% CI, 0.75–0.93; P<0.001) in pts with chemotherapy-naive mCRPC. It is unknown whether ENZA DOT can affect OS. This post hoc analysis of PREVAIL evaluated the relationship between ENZA DOT and OS and prognostic factors related to OS, long-term response (LTR), and early treatment failure (ETF).

Methods

In PREVAIL, pts were randomized 1:1 to ENZA 160 mg/d or placebo, both with androgen deprivation therapy. The primary endpoint of this post hoc analysis was the relationship between ENZA DOT and OS based on 5-yr OS data. Secondary endpoints were prognostic factors related to OS, LTR (DOT ≥18 mo), and ETF (DOT <6 mo). OS was assessed using a log-rank test stratified by DOT. Multivariate Cox regression analyses assessed the relationship between DOT and OS and identified prognostic factors related to OS, LTR, and ETF.

Results

Pts treated with ENZA (N=871) were stratified by DOT (<6 mo [n=121; 14%], 6 to <12 mo [n=159; 18%], 12 to <18 mo [n=161; 18%], and ≥18 mo [n=430; 49%]). Demographic characteristics were balanced across DOT subgroups. Longer ENZA DOT was associated with prolonged OS (P<0.0001); the median OS was 58.7 mo for pts with DOT ≥18 mo and 14.0 mo for pts with DOT <6 mo (HR, 0.10; 95% CI, 0.08–0.12; P<0.0001). Prognostic factors for OS were DOT, baseline prostate-specific antigen (PSA) and hemoglobin levels, disease distribution, and Gleason score. Fewer pts in the ENZA arm had ETF vs placebo (14% vs 63%) and 5-fold more pts achieved LTR (49% vs 10%). Compared with pts with ETF, pts with LTR trended toward better baseline health (ECOG status 0; higher hemoglobin levels; Brief Pain Inventory score 0–1), lower baseline PSA levels, and baseline corticosteroid use ≤7 days.

Conclusions

This post hoc analysis suggests ENZA DOT may predict OS. Pts with mCRPC who have good baseline health and low PSA levels can experience long-term disease control with ENZA, with a median OS of ∼5 y. Because confounding factors may affect treatment outcomes, further studies are needed to validate these results.

Clinical trial identification

NCT01212991.

Editorial acknowledgement

Medical writing/editorial support was provided by Kalpana Vijayan, PhD from Peloton Advantage, LLC, an OPEN Health company.

Legal entity responsible for the study

Astellas Pharma Inc.

Funding

Astellas Pharma Inc. and Pfizer Inc.

Disclosure

E. Chiong: Financial Interests, Personal, Advisory Board: Janssen, Bayer, AstraZeneca, Ipsen, Amgen, Ferring, Novartis, DCH Auriga; Financial Interests, Personal, Speaker, Consultant, Advisor, Travel support: Astellas. B. Tombal: Non-Financial Interests, Institutional, Advisory Role: Astellas; Non-Financial Interests, Institutional, Advisory Board: Bayer, Farring, Janssen, Myovant, Pfizer; Financial Interests, Institutional, Leadership Role, Leadership or Fiduciary Role: EORTC, ISSECAM. M. Lian, G. Gourgioti, A. Dhar, Z. Xiao: Financial Interests, Institutional, Full or part-time Employment: Astellas. T. Beer: Financial Interests, Institutional, Research Grant, Grants or Contracts: Alliance Foundation Trials, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Endocyte Inc./Advanced Accelerator Applications (AAA), Freenome, GSK, Grail Inc, Harpoon Therapeutics, Janssen Research & Development, Medivation, Inc., Sotio, Theraclone Sciences/OncoResponse, Zenith Epigenetics; Financial Interests, Institutional, Financially compensated role, Consulting Fees: Arvinas, Astellas Pharma, Bayer, Bristol-Myers Squibb Constellation, Clovis Oncology, Grail Inc, Janssen, Merck, Myovant Sciences, Novartis, Pfizer, Sanofi, Tolero. All other authors have declared no conflicts of interest.