Talazoparib Improves Overall Survival in Metastatic CRPC

An analysis of a phase III trial presented at this year’s American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium showed that adding the PARP inhibitor talazoparib (Talzenna) to enzalutamide (Xtandi) significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) in patients with metastatic castration-resistant prostate cancer (CRPC).

In this exclusive MedPage Today video, Neeraj Agarwal, MD, of the Huntsman Cancer Institute at the University of Utah in Salt Lake City, discusses the findings and their implications for clinical practice.

Following is a transcript of his remarks:

The TALAPRO-2 trial is a phase III trial comparing the efficacy of enzalutamide plus talazoparib, a PARP inhibitor, with enzalutamide plus placebo in patients with metastatic castration-resistant prostate cancer.

We previously reported the primary endpoint on radiographic progression-free survival in 2023. At the 2025 ASCO GU Symposium, we reported the overall survival data from this study. Just to let you know that overall survival was a key alpha-protected secondary endpoint, which means the trial was powered to look for overall survival benefit.

So if we look at the rPFS first, there was a 14-month improvement in radiographic progression-free survival by adding talazoparib to enzalutamide. The hazard ratio was 0.67, which translates into 33% reduction in risk of progression or death. It’s a very meaningful improvement in radiographic progression-free survival because that basically means we are delaying the pain, suffering, fractures in the bones in patients with metastatic CRPC because these symptoms or these complications are associated with progression of castration-resistant disease.

If you come to the overall survival endpoint, which was the focus of this presentation, there was a 20% reduction in risk of death, with about a 9-month improvement in overall survival in patients who received talazoparib in addition to enzalutamide. If you look at the overall survival in the talazoparib arm, it was 46 months, and it was 37 months in patients who only received enzalutamide.

If you look at subgroups such as patients with high Gleason score, patients who had received abiraterone or docetaxel — this is relatively a small number of patients, only 21% of these patients received abiraterone-docetaxel in the hormone-sensitive setting — or whether patients had de novo disease in the past, or metastatic disease, all patients seem to benefit with the combination.

Then a question often arises about patients who did not have these alterations, so we performed an analysis where we looked for HRR [homologous recombination repair] gene alteration status by both [circulating tumor] ctDNA and tumor tissue testing. There was about a 9-month improvement in overall survival with a hazard ratio of 0.78, favoring the talazoparib arm. So when you add talazoparib to enzalutamide, it seemed to benefit patients who do not have HRR gene alterations or who do not have BRCA1 or BRCA2 alterations.

If you look at time to chemotherapy, that was also prolonged or delayed in patients who received talazoparib. The hazard ratio was 0.56, favoring the talazoparib arm.

If we look at side effects, we didn’t see any new safety signal. We reported previously, like 2 years ago, two cases, one case of MDS [myelodysplastic syndrome] and one case of acute leukemia and we did not see any new cases of MDS or leukemia after a 4-year follow-up. So after 2 additional years of follow-up, we did not see any of those side effects.

So I’d like to conclude that TALAPRO-2 is the first PARP inhibitor plus ARPI [androgen receptor pathway inhibitor] combination study to show a statistically significant and clinically meaningful improvement in overall survival versus standard-of-care active control of enzalutamide in both unselected patients, like the intention-to-treat patient population, as well as patients who had HRR gene alterations. Radiographic progression-free survival was significantly delayed by about 14 months with talazoparib in unselected patients, which is quite meaningful because this means delaying of suffering in the castration resistance setting, and we did not see any new safety signal.

With that, I would like to conclude that our data support talazoparib plus enzalutamide as a standard-of-care treatment option for patients who are diagnosed to have [metastatic] CRPC.

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