Genomic Biomarker Testing in mCRPC

The phase III TALAPRO-2 trial established that combining talazoparib (TALA) with enzalutamide significantly extends progression-free survival (PFS) and overall survival in metastatic castration-resistant prostate cancer (mCRPC) patients.

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).

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.

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.

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).

The absence of direct comparisons between talazoparib plus enzalutamide (TALA+ENZA) and current standard of care hinders evaluating their relative efficacy for first-line (1 L) metastatic castration resistant prostate cancer (mCRPC).

We present a systematic review and meta-analysis of randomized clinical trials (RCTs) with PARPi either as monotherapy or in combination with an androgen receptor-targeted agent (ARTA) in first- and second-line settings.

Prostate cancer (PCa) is the second most common cancer diagnosis among men worldwide, with poor prognosis in its advanced stage. Treatment strategies have evolved, including the use of androgen receptor pathway inhibitors (ARPIs) and poly (ADP-ribose) polymerase inhibitors (PARPis).

Without head-to-head trials between talazoparib+enzalutamide (TALA + ENZA), olaparib+abiraterone acetate (OLAP + AAP), and niraparib plus AAP (NIRA + AAP) the ability to evaluate their relative efficacy as first-line (1 L) treatment in metastatic castration-resistant prostate cancer (mCRPC) is limited.

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).

Talazoparib plus enzalutamide (TALA + ENZA) has demonstrated antitumor activity in the phase 3 clinical trial (TALAPRO-2; NCT03395197) as first-line (1L) therapy in men with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC).

Around 25% of patients with advanced prostate cancer harbor alterations in the homologous recombination/DNA damage repair (HRR) pathway. Inhibiting poly (ADP-ribose) polymerase (PARP) in these patients leads to synthetic lethality, making PARP inhibitors (PARPi), including talazoparib, a promising treatment for metastatic castration-resistant prostate cancer (mCRPC) and potentially for metastatic hormone-sensitive prostate cancer (mHSPC).

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.

Preclinical evidence has suggested an interplay between the androgen receptor, which largely drives the growth of prostate cancer cells, and poly(ADP-ribose) polymerase. This association provides a rationale for their co-inhibition for the treatment of metastatic castration-resistant prostate cancer (mCRPC), an area of unmet medical need.

Prostate cancer (PCa) is the most common cancer in men worldwide. Despite better and more intensive treatment options in earlier disease stages, a large subset of patients still progress to metastatic castration-resistant PCa (mCRPC).

To compare radiographic progression-free survival (rPFS), overall survival (OS), and treatment-emergent adverse events (TEAEs) among metastatic castrate-resistant prostate cancer (mCRPC) patients receiving combination first-line poly(ADP-ribose) polymerase inhibitors (PARPi) plus androgen receptor axis-targeted agents (ARATs) versus placebo/ARAT.

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).

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.

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.