Final 5-yr Survival analysis in the P... - Advanced Prostate...

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Final 5-yr Survival analysis in the PREVAIL trial.

pjoshea13 profile image
6 Replies

New study below [1].

"In the PREVAIL study, enzalutamide significantly improved clinical outcomes versus placebo in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC)."

Enzalutamide arm: n = 689; placebo arm: n = 693.

"At the 5-yr data cutoff, 1382 of 1717 (80%) men had died. Enzalutamide reduced the hazard of death by 17% (hazard ratio 0.83 ..., despite 65%, 54%, and 43% of placebo-treated patients receiving subsequent docetaxel, abiraterone, and enzalutamide, respectively."

"Median overall survival was 36 mo ... in the enzalutamide arm versus 31 mo ... in the placebo arm, with a median follow-up of 69 mo."

"A higher incidence of fatal treatment-emergent adverse events was observed with enzalutamide (6.9% vs 3.8%), with an increase in fatal cardiovascular events (1.6% vs 0.4%)."

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/325...

Eur Urol

. 2020 Jun 9;S0302-2838(20)30329-8. doi: 10.1016/j.eururo.2020.04.061. Online ahead of print.

Five-year Survival Prediction and Safety Outcomes With Enzalutamide in Men With Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer From the PREVAIL Trial

Andrew J Armstrong 1 , Ping Lin 2 , Bertrand Tombal 3 , Fred Saad 4 , Celestia S Higano 5 , Anthony M Joshua 6 , Teresa Parli 7 , Brad Rosbrook 8 , Steve van Os 9 , Tomasz M Beer 10

Affiliations collapse

Affiliations

1 Division of Medical Oncology and Urology, Duke Cancer Institute, Duke University, Durham, NC, USA. Electronic address: andrew.armstrong@duke.edu.

2 Biostatistics, Pfizer Inc., San Francisco, CA, USA.

3 Urology, Cliniques Universitaires Saint-Luc, Brussels, Belgium.

4 Division of Urology and Urologic Oncology, Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada.

5 Medical Oncology, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

6 Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, New South Wales, Australia.

7 Clinical Development, Pfizer Inc., San Francisco, CA, USA.

8 Biostatistics, Pfizer Inc., San Diego, CA, USA.

9 Biostatistics, Astellas Pharma Europe BV, Leiden, The Netherlands.

10 Hematology/Medical Oncology, OHSU Knight Cancer Institute Oregon Health & Science University, Portland, OR, USA.

PMID: 32527692 DOI: 10.1016/j.eururo.2020.04.061

Abstract

Background: In the PREVAIL study, enzalutamide significantly improved clinical outcomes versus placebo in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC).

Objective: To evaluate long-term benefits and risks of enzalutamide in the final prespecified PREVAIL analysis.

Design, setting, and participants: We conducted a final 5-yr survival analysis of PREVAIL in men with chemotherapy-naïve mCRPC from the enzalutamide (n = 689) and placebo (n = 693) arms.

Outcome measurements and statistical analysis: Predictors of the primary outcome of overall survival were estimated using the Kaplan-Meier method. Long-term adverse events over time were analyzed.

Results and limitations: At the 5-yr data cutoff, 1382 of 1717 (80%) men had died. Enzalutamide reduced the hazard of death by 17% (hazard ratio 0.83; 95% confidence interval [CI] 0.75-0.93; p < 0.001), despite 65%, 54%, and 43% of placebo-treated patients receiving subsequent docetaxel, abiraterone, and enzalutamide, respectively. Median overall survival was 36 mo (95% CI 34-38) in the enzalutamide arm versus 31 mo (95% CI 29-34) in the placebo arm, with a median follow-up of 69 mo. Prognostic modeling showed 5-yr survival rates of 42%, 24%, and 5% for low-, intermediate-, and high-risk groups, respectively. Greater degrees of confirmed prostate-specific antigen declines (≤3 mo) were associated with greater 5-yr survival. A higher incidence of fatal treatment-emergent adverse events was observed with enzalutamide (6.9% vs 3.8%), with an increase in fatal cardiovascular events (1.6% vs 0.4%).

Conclusions: With >5 yr of follow-up, enzalutamide continued to demonstrate improved survival in patients with mCRPC despite crossover and multiple subsequent effective therapies, balanced against a slightly higher rate of fatal cardiovascular events. PREVAIL is registered on ClinicalTrials.gov as NCT01212991.

Patient summary: We report a maintained long-term survival benefit with enzalutamide and risks with >5 yr of enzalutamide treatment and follow-up in men with metastatic prostate cancer, and identify groups of men with widely different outcomes based on clinical factors.

Keywords: Enzalutamide; Metastatic castration-resistant prostate cancer; Multivariable model; Overall survival; Prostate-specific antigen; Safety.

Copyright © 2020. Published by Elsevier B.V.

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Dett profile image
Dett

Could you please clarify your comments?

ctarleton profile image
ctarleton

Outside of this Trial I added Xtandi about 10 months after becoming castrate resistant, and while having a PSA of 95.0 with around 10 confirmed "hot spots" per a GA-68 PSMA PET scan. I have had a not perfect (but relatively good, considering) Overall Survival that's already in excess of the 36 month Mean OS for Xtandi. "I'll take it."

Rocketman1960 profile image
Rocketman1960 in reply toctarleton

Exactly! Me too.

So Enzalutamide provides a benefit but hardly a cure. Not very encouraging. Yikes.

Rocketman1960 profile image
Rocketman1960 in reply to

Xtandi was never a cure. It simply kicks the can down the road. Hoping more great drugs come online to kick the can further.

DarkEnergy profile image
DarkEnergy in reply toRocketman1960

Yep, don't forget the revenue stream. I'm not a conspiracy nut, but Clinical Research does have a time limitation to produce results...

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