Final 5-yr Survival analysis in the PREVAIL trial.

[pjoshea13]

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: [e-mail].

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.

[Dett]

Could you please clarify your comments?

[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 in reply to ctarleton]

Exactly! Me too.

[Hidden]

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

[Rocketman1960 in reply to Hidden]

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 in reply to Rocketman1960]

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