Talazoparib plus enzalutamide in men with metastatic castration-resistant prostate cancer: final overall survival results from the randomised, placebo-controlled, phase 3 TALAPRO-2 trial.

Background: The primary analysis of this phase 3 trial combining talazoparib with enzalutamide demonstrated significantly improved radiographic progression-free survival (rPFS) versus enzalutamide plus placebo in patients with metastatic castration-resistant prostate cancer unselected for homologous recombination repair (HRR) gene alterations. Overall survival data were immature at that time. Here we report the final prespecified overall survival analysis, an updated descriptive analysis of rPFS, and safety in the cohort unselected for HRR gene alterations.

Talazoparib plus enzalutamide in men with HRR-deficient metastatic castration-resistant prostate cancer: final overall survival results from the randomised, placebo-controlled, phase 3 TALAPRO-2 trial.

Background: Metastatic castration-resistant prostate cancer remains incurable and is particularly aggressive in patients with alterations in DNA damage repair genes involved directly or indirectly in homologous recombination repair (HRR). In the primary analysis of TALAPRO-2, talazoparib plus enzalutamide significantly improved radiographic progression-free survival (rPFS) versus enzalutamide plus placebo in patients with metastatic castration-resistant prostate cancer harbouring HRR gene alterations. At primary analysis, overall survival was immature.

Safety and Tolerability of Relugolix in Combination with Abiraterone or Apalutamide for Treatment of Patients with Advanced Prostate Cancer: Data from a 52-Week Clinical Trial.

Background: The gonadotropin-releasing hormone (GnRH) receptor antagonist relugolix is the only oral androgen deprivation therapy (ADT) indicated for advanced prostate cancer (aPC). Combining ADT with androgen receptor signaling inhibitors (ARSIs) has shown improved clinical outcomes.

Objective: To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of relugolix in combination with ARSIs in patients with aPC.

First-line talazoparib plus enzalutamide versus placebo plus enzalutamide in men with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: patient-reported outcomes from the randomised, double-blind, placebo-controlled, phase 3 TALAPRO-2 trial.

Background: In the phase 3 TALAPRO-2 trial, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide in men with metastatic castration-resistant prostate cancer harbouring alterations in genes involved in homologous recombination repair (HRR). We aimed to assess patient-reported outcomes in patients with HRR-deficient metastatic castration-resistant prostate cancer in TALAPRO-2.

Methods: TALAPRO-2 is a randomised, double-blind, placebo-controlled, phase 3 trial conducted at 223 hospitals, cancer centres, and medical centres in 26 countries worldwide.

First-line talazoparib plus enzalutamide versus placebo plus enzalutamide for metastatic castration-resistant prostate cancer: patient-reported outcomes from the randomised, double-blind, placebo-controlled, phase 3 TALAPRO-2 trial.

Background: Patients with metastatic castration-resistant prostate cancer have poor prognoses, underscoring the need for novel therapeutic strategies. First-line talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide in men with metastatic castration-resistant prostate cancer in the phase 3 TALAPRO-2 study. We aimed to evaluate patient-reported outcomes in the all-comers cohort of TALAPRO-2, which included patients with and without alterations in homologous recombination repair (HRR) genes.

Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: Safety analyses from the randomized, placebo-controlled, phase III TALAPRO-2 study.

Background: This detailed analysis further characterizes the safety profile of talazoparib plus enzalutamide in the ongoing randomized, phase III TALAPRO-2 study in patients with metastatic castration-resistant prostate cancer (mCRPC). In both the all-comers and homologous recombination repair (HRR)-deficient populations, talazoparib plus enzalutamide significantly improved radiographic progression-free survival compared with placebo plus enzalutamide.

Methods: The talazoparib plus enzalutamide safety populations in TALAPRO-2 included 398 patients from cohort 1 (all-comers, unselected for HRR gene alterations) and 198 patients from the combined HRR-deficient population (patients from the all-comers population with HRR gene alterations plus subsequently enrolled patients with HRR gene alterations; cohort 2).

Plain language summary of the results from the TALAPRO-2 study: Talazoparib plus enzalutamide versus placebo plus enzalutamide for patients with advanced prostate cancer.

What Is This Summary About?: This summary describes the results from the TALAPRO-2 research study (also known as a clinical trial). The TALAPRO-2 study tested the combination of two medicines called talazoparib plus enzalutamide. This combination of medicines was used as the first treatment for adult patients with metastatic castration-resistant prostate cancer.

First-line combination treatment with PARP and androgen receptor-signaling inhibitors in HRR-deficient mCRPC: Applying clinical study findings to clinical practice in the United States.

Introduction: Metastatic castration-resistant prostate cancer (mCRPC) remains incurable and develops from biochemically recurrent PC treated with androgen deprivation therapy (ADT) following definitive therapy for localized PC, or from metastatic castration-sensitive PC (mCSPC). In the mCSPC setting, treatment intensification of ADT plus androgen receptor (AR)-signaling inhibitors (ARSIs), with or without chemotherapy, improves outcomes vs ADT alone. Despite multiple phase 3 trials demonstrating a survival benefit of treatment intensification in PC, there remains high use of ADT monotherapy in real-world clinical practice.

Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial.

Background: Co-inhibition of poly(ADP-ribose) polymerase (PARP) and androgen receptor activity might result in antitumour efficacy irrespective of alterations in DNA damage repair genes involved in homologous recombination repair (HRR). We aimed to compare the efficacy and safety of talazoparib (a PARP inhibitor) plus enzalutamide (an androgen receptor blocker) versus enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods: TALAPRO-2 is a randomised, double-blind, phase 3 trial of talazoparib plus enzalutamide versus placebo plus enzalutamide as first-line therapy in men (age ≥18 years [≥20 years in Japan]) with asymptomatic or mildly symptomatic mCRPC receiving ongoing androgen deprivation therapy.

Plain language summary of the design of the TALAPRO-2 study comparing talazoparib and enzalutamide versus enzalutamide and placebo in men with metastatic castration-resistant prostate cancer.

What Is This Summary About?: This summary describes the design of an ongoing research study (also known as a clinical trial) called TALAPRO-2. The TALAPRO-2 trial is testing the combination of two medicines called talazoparib and enzalutamide as a first treatment in adult men with metastatic castration-resistant prostate cancer. The study began in December 2017 and has enrolled 1037 adult men with metastatic castration-resistant prostate cancer from 26 countries.

Talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer: TALAPRO-2 phase III study design.

PARP inhibitors in combination with androgen receptor-targeted therapy have demonstrated potential in the treatment of metastatic castration-resistant prostate cancer (mCRPC). Here, we describe the design and rationale of the multinational, phase III, two-part TALAPRO-2 study comparing talazoparib plus enzalutamide versus placebo plus enzalutamide as a first-line treatment for patients with mCRPC with or without DNA damage response (DDR) alterations. This study has two co-primary end points: radiographic progression-free survival (rPFS) by blinded independent clinical review in all-comers (cohort 1) and in patients with DDR alterations (cohort 2).

Enzalutamide versus bicalutamide in patients with nonmetastatic castration-resistant prostate cancer: a prespecified subgroup analysis of the STRIVE trial.

Background: In the phase 2, randomized, double-blind STRIVE trial, enzalutamide significantly reduced the risk of prostate cancer progression or death versus bicalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) and nonmetastatic CRPC (nmCRPC). The objective of this protocol-specified subgroup analysis of STRIVE was to investigate the benefit of enzalutamide versus bicalutamide specifically in patients with nmCRPC.

Methods: Patients (N = 139) were stratified by disease stage and randomized to enzalutamide 160 mg/day plus androgen deprivation therapy (ADT; n = 70) or bicalutamide 50 mg/day plus ADT (n = 69).

Optimizing the management of castration-resistant prostate cancer patients: A practical guide for clinicians.

Background: Advanced prostate cancer (PC) patients, especially those with metastatic prostate cancer (mPC), often require complex management pathways. Despite the publication of clinical practice guidelines by leading urological and oncological organizations that provide a substantial and comprehensive framework, there are numerous clinical scenarios that are not always addressed, especially as new treatments become available, new imaging modalities are developed, and advances in genetic testing continue.

Methods: A 14-member expert review panel comprised of urologists and medical oncologists were chosen to provide guidance on addressing specific topics and issues regarding metastatic castration-resistant prostate cancer (mCRPC) patients.

Effect of Enzalutamide plus Androgen Deprivation Therapy on Health-related Quality of Life in Patients with Metastatic Hormone-sensitive Prostate Cancer: An Analysis of the ARCHES Randomised, Placebo-controlled, Phase 3 Study.

Background: In the ARCHES study in metastatic hormone-sensitive prostate cancer (mHSPC), enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) versus ADT alone.

Objective: To evaluate patient-reported outcomes (PROs) to week 73.

Design, Setting, And Participants: ARCHES (NCT02677896) was a randomised, double-blind, placebo-controlled, phase 3 study in mHSPC patients.