Talzenna Plus Xtandi Delays Prostate Cancer Progression

A combination of Talzenna (talazoparib) and Xtandi (enzalutamide) significantly improved outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC), according to findings from the phase 3 TALAPRO-2 trial. The regimen met its primary end point by extending radiographic progression-free survival (rPFS), meaning patients lived longer without their cancer worsening on imaging scans.

In the final analysis, the combination reduced the risk of disease progression or death by 37% compared with Xtandi alone. Median rPFS was not reached in the combination arm at the time of analysis, compared with 21.9 months for patients receiving Xtandi plus placebo, highlighting a meaningful delay in disease progression.

“Current treatment approaches leave many patients with HRR gene-mutated metastatic castration-sensitive prostate cancer vulnerable to early disease progression,” said Dr. Neeraj Agarwal, professor and Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute at the University of Utah, and global lead investigator for TALAPRO-3. “The TALAPRO-3 results demonstrate that treatment with Talzenna in combination with Xtandi earlier in the disease course significantly extends the time patients can live without their cancer worsening.”

Key findings from the TALAPRO-2 trial

The TALAPRO-2 study demonstrated consistent benefits across multiple patient groups. Improvements in rPFS were observed in patients with homologous recombination repair (HRR) gene mutations as well as those without or with unknown mutation status.

Beyond delaying disease progression, the combination also improved several secondary outcomes. These included higher response rates, greater reductions in prostate-specific antigen (PSA) levels, and a longer time before PSA levels began rising again. Patients receiving the combination also experienced a delay in the need for chemotherapy and other subsequent treatments.

Importantly, patient-reported quality of life was maintained. The median time to meaningful deterioration in overall health status was longer with the combination compared with Xtandi alone.

The safety profile of the regimen was consistent with what is already known about each drug. Common side effects included anemia, fatigue, and low blood cell counts, although these were generally manageable with supportive care and dose adjustments.

Understanding mCRPC

Metastatic castration-resistant prostate cancer is an advanced form of prostate cancer that continues to grow despite treatments designed to lower testosterone levels. This stage of disease is associated with a poorer prognosis and limited treatment options.

Approximately 10% to 20% of patients with prostate cancer develop mCRPC within approximately five to seven years of their initial diagnosis. Over the past decade, androgen receptor pathway inhibitors such as Xtandi have improved outcomes, although many patients eventually experience disease progression.

Talzenna belongs to a class of drugs known as PARP inhibitors, which target cancer cells with defects in DNA repair pathways. Combining a PARP inhibitor with hormone therapy is designed to enhance treatment effectiveness by attacking cancer through multiple mechanisms.

TALAPRO-2 trial design and methods

TALAPRO-2 is a global, randomized, double-blind, placebo-controlled phase 3 trial evaluating Talzenna plus Xtandi versus placebo plus Xtandi in patients with mCRPC.

Participants were assigned to receive either the combination therapy or standard treatment with Xtandi alone. The primary endpoint was radiographic progression-free survival, assessed by imaging scans to determine how long patients lived without disease worsening.

The study also evaluated several secondary endpoints, including overall survival, PSA response, and time to additional therapies. At the time of the initial analysis, overall survival data were still immature, although a favorable trend was observed.

The trial included a broad population of patients with metastatic castration-resistant prostate cancer. Importantly, patients were enrolled regardless of HRR mutation status, allowing researchers to evaluate the benefit of the combination in both biomarker-selected and unselected groups.

The study design included subgroups of patients with HRR gene mutations and those without these alterations. This approach helped demonstrate that the treatment benefit extended across clinically relevant populations.

Additional findings and what they mean for patients

The TALAPRO-2 results highlight the potential for Talzenna plus Xtandi to become a practice-changing option in mCRPC. In addition to delaying disease progression, the combination showed improvements in multiple clinically meaningful endpoints, reinforcing its potential role in earlier lines of therapy.

Although overall survival data were not yet fully mature at the time of the primary analysis, later updates have suggested a survival benefit, further supporting the combination’s clinical value.

References

1. “TALZENNA Plus XTANDI Significantly Improves Radiographic Progression-Free Survival in Metastatic Prostate Cancer,” by Pfizer Inc. News release; March 19, 2026.

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