PREVAIL Trial [Xtandi] - low-PSA cases

[pjoshea13]

New study below.

The study looked at men with metastatic CRPC who had not received Taxotere, etc.

It was limited to low PSA cases - less than 10 ng/ml - i.e. due to "early stage in the natural history of castration-resistant prostate cancer disease progression (low-volume disease), low prostate-specific antigen-producing disease, or disease less dependent on androgen receptor biology (high-volume disease)"

"Of 1717 patients enrolled in PREVAIL, 242 (14.1%) had low baseline prostate-specific antigen, including 110 men with high-volume disease."

"Enzalutamide decreased the risk of radiographic progression relative to placebo (hazard ratio 0.20 ...) in patients with a low baseline prostate-specific antigen, irrespective of tumor burden (high-volume disease, hazard ratio 0.17 ..; low-volume disease, hazard ratio 0.25 ..)."

"Chemotherapy-naïve men with metastatic castration-resistant prostate cancer and low baseline prostate-specific antigen irrespective of disease burden may benefit from enzalutamide, indicating that targeting the androgen-receptor signaling pathway is a therapeutic option in similar patients."

-Patrick

ncbi.nlm.nih.gov/pubmed/287...

J Urol. 2017 Jul 20. pii: S0022-5347(17)77187-X. doi: 10.1016/j.juro.2017.07.071. [Epub ahead of print]

Clinical Outcomes of Chemotherapy-Naïve Men with Metastatic Castration-Resistant Prostate Cancer and Low Baseline PSA Treated with Enzalutamide vs Placebo.

Taplin ME1, Armstrong AJ2, Lin P3, Krivoshik A4, Phung4, Parli T3, Tombal B5, Beer TM6.

Author information

1

Dana-Farber Cancer Institute, Boston, Massachusetts. Electronic address: [e-mail].

2

Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.

3

Medivation, Inc., San Francisco, California (Medivation was acquired by Pfizer, Inc., in September 2016).

4

Astellas Pharma Global Development, Inc., Northbrook, Illinois.

5

Cliniques universitaires Saint-Luc, Brussels, Belgium.

6

OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.

Abstract

PURPOSE:

Metastatic castration-resistant prostate cancer with low baseline prostate-specific antigen represents an early stage in the natural history of castration-resistant prostate cancer disease progression (low-volume disease), low prostate-specific antigen-producing disease, or disease less dependent on androgen receptor biology (high-volume disease). We analyzed outcomes in men with low prostate-specific antigen and high disease burden who received the oral androgen-receptor inhibitor enzalutamide in the PREVAIL study.

MATERIALS AND METHODS:

In this exploratory analysis, low baseline prostate-specific antigen was defined as a level of less than 10 ng/ml. Post-hoc analyses included radiographic progression-free survival and overall survival in the once-daily enzalutamide and placebo arms. Patients were stratified post hoc by high-volume disease (more than 4 bone metastasis and/or visceral disease) and low-volume disease (4 or less bone metastases with no visceral disease).

RESULTS:

Of 1717 patients enrolled in PREVAIL, 242 (14.1%) had low baseline prostate-specific antigen, including 110 men with high-volume disease. Enzalutamide decreased the risk of radiographic progression relative to placebo (hazard ratio 0.20, 95% CI 0.10-0.42) in patients with a low baseline prostate-specific antigen, irrespective of tumor burden (high-volume disease, hazard ratio 0.17, 95% CI 0.06-0.51; low-volume disease, hazard ratio 0.25, 95% CI 0.09-0.70). Median overall survival was not reached for both treatment arms for patients with a low baseline prostate-specific antigen.

CONCLUSIONS:

Chemotherapy-naïve men with metastatic castration-resistant prostate cancer and low baseline prostate-specific antigen irrespective of disease burden may benefit from enzalutamide, indicating that targeting the androgen-receptor signaling pathway is a therapeutic option in similar patients.

Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

androgen receptor; castration-resistant prostatic neoplasms; enzalutamide; prostate-specific antigen; treatment efficacy

PMID: 28736322 DOI: 10.1016/j.juro.2017.07.071

[rococo]

Castrate insensitive or ultrasenitive to T is the question and if the latter than what's driving the cancer. Might it be the small amt. Of T. Made by these clonal cells that dosent get into the bloodstream whose ultrasensitive androgen receptors are targeted by xtandi.? Rocco