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Related Experiment Video

Updated: Jun 2, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

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Published on: March 6, 2018

PARP and Androgen-Signaling Inhibition plus ADT in Metastatic Prostate Cancer.

Neeraj Agarwal¹, Nobuaki Matsubara², Arun A Azad³

¹Huntsman Cancer Institute, University of Utah, Salt Lake City.

The New England Journal of Medicine

|June 1, 2026

Summary

This summary is machine-generated.

Adding talazoparib to enzalutamide significantly improved progression-free survival in patients with metastatic prostate cancer harboring DNA repair gene alterations. While overall survival showed a positive trend, increased serious adverse events were noted with talazoparib.

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Area of Science:

Oncology
Genetics
Pharmacology

Background:

Previous trials indicated talazoparib plus enzalutamide benefits metastatic prostate cancer patients with specific gene alterations.
Androgen pathway modulation-resistant prostate cancer (formerly castration-resistant) showed improved outcomes with this combination therapy.

Purpose of the Study:

To assess the efficacy and safety of talazoparib combined with enzalutamide in metastatic prostate cancer patients with homologous recombination repair (HRR) gene alterations.
To evaluate imaging-based progression-free survival (PFS) and overall survival (OS) as primary and secondary endpoints.

Main Methods:

Phase 3, double-blind, randomized trial comparing talazoparib plus enzalutamide versus placebo plus enzalutamide.
Patients with metastatic androgen pathway modulation-sensitive (APMS) prostate cancer and HRR gene alterations were enrolled.
Stratification by disease status, volume, and BRCA mutation status; primary endpoint was investigator-assessed PFS.

Main Results:

Talazoparib significantly improved 3-year PFS (77% vs. 56%) and showed a positive trend in 3-year OS (78% vs. 72%).
Serious adverse events were more frequent in the talazoparib group (42% vs. 32%).
Anemia was the most common grade 3+ adverse event (51%) in the talazoparib arm; two treatment-related deaths occurred.

Conclusions:

Talazoparib plus enzalutamide demonstrates superior PFS compared to placebo plus enzalutamide in metastatic APMS prostate cancer with HRR alterations.
Increased incidence of serious adverse events, particularly anemia, necessitates careful monitoring.
The combination therapy represents a significant advancement for this patient population.