Real-World Use of Talazoparib Plus Enzalutamide and HR Testing Trends in Prostate Cancer

In this interview with Pharmacy Times, Andrew Osterland, PharmD, MS Research Scientist, Real-World Research, Ontada, discusses findings from a real-world analysis evaluating talazoparib (Talzenna; Pfizer) plus enzalutamide (Xtandi; Pfizer, Astellas) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated in community oncology settings. He explains that the combination is largely being used in alignment with its FDA-approved indication for HR-mutated mCRPC, although treatment sequencing and prior androgen receptor pathway inhibitor exposure varied across patients. He also highlights the growing importance of earlier HR biomarker testing in prostate cancer management, particularly as NCCN guidelines increasingly support broader testing to guide targeted therapy decisions and clinical trial eligibility.

Pharmacy Times: Your research evaluated real-world use of talazoparib plus enzalutamide in metastatic castration-resistant prostate cancer. What were the most important findings regarding how this combination is being used in the community oncology setting?

Andrew Osterland, PharmD: We conducted a retrospective real-world analysis using both structured and unstructured data from the EHR of a large community oncology network, and we identified a total of 52 patients who initiated talazoparib plus enzalutamide between its FDA approval in June 2023 and December 2024.

Among eligible patients, we observed that talazoparib plus enzalutamide is being adopted in the community oncology setting largely in line with its approved indication, which is for patients with HR-mutated metastatic castration-resistant prostate cancer, or mCRPC. That said, we did see some variability in treatment sequencing. There were 43% of patients who initiated talazoparib plus enzalutamide after 1 or more prior treatments in the mCRPC setting, and 85% of patients had prior treatment with an androgen receptor pathway inhibitor, or ARPI.

That likely reflects the complexity of real-world decision-making for newly approved treatments. Overall, we’re seeing that this regimen is being integrated into community practice while also being adapted based on individual patient histories.

Pharmacy Times: How did the patients receiving talazoparib plus enzalutamide in real-world practice compare with those enrolled in clinical trials, and were there any trends that surprised you?

Osterland: As expected, the real-world patient population represented a more diverse group than those typically enrolled in clinical trials. There was also a small proportion of patients with poor performance status who would typically be excluded from clinical trials. We also saw a relatively high metastatic burden in patients with prior ARPI exposure, most of whom would not have been eligible based on some of the stricter eligibility criteria used in clinical trials.

These differences will be important to recognize in future studies as we begin to evaluate the clinical effectiveness outcomes of talazoparib plus enzalutamide. Additionally, we looked at HR mutations and observed that the most commonly mutated genes included BRCA2, CDK12, ATM, and CHEK2. That distribution was relatively consistent with what was observed in the clinical trial population.

At the same time, there was some variability in HR testing patterns and in the documentation of results within the EHR that allowed us to capture them. That highlights an ongoing gap between clinical trials and real-world practice settings.

Pharmacy Times: Your second analysis focused on homologous recombination repair (HRR) testing in metastatic castration-sensitive prostate cancer. Why is earlier biomarker testing becoming increasingly important in prostate cancer management today?

Osterland: Earlier testing does align with current NCCN guidelines, which recommend testing for HR mutations in all patients with metastatic prostate cancer, along with some patients with high- or very high-risk localized or regional disease. Additionally, patients with a family history of certain cancers, including prostate cancer or familial cancer risk mutations, are also recommended to receive testing.

This ensures that providers have the information they need to make timely and informed treatment decisions, particularly regarding the use of targeted therapies and clinical trial eligibility.

Pharmacy Times: From a pharmacist and community oncology perspective, what are some of the biggest barriers to broader HRR testing adoption, and how can oncology teams help improve implementation in routine practice?

Osterland: We have seen that there are several factors that continue to limit the broader adoption of HR testing. Previous studies highlighted in our poster found that testing is more likely among patients with high-risk clinical features, such as a family history of prostate cancer or a Gleason score of 8 or higher. In contrast, HR testing was less common among older patients, those with poor performance status, and patients facing socioeconomic barriers, including disparities associated with insurance type or income.

Those findings were primarily observed in the mCRPC setting. Our study builds on that with additional information from the mCSPC setting, and we observed similar themes in our analysis. Patients with more advanced disease, such as de novo metastatic disease and higher PSA levels, were more likely to undergo testing, whereas lower testing rates were seen among patients aged 70 years or older.

Addressing these gaps will likely require more standardized and proactive approaches. Reflex testing at the time of metastatic diagnosis would be aspirational, and increased education through studies such as this may also help improve adoption. Pharmacists can play an important role in operationalizing testing workflows, tracking results, and ensuring that biomarker findings are appropriately integrated into treatment decisions and ongoing monitoring. These types of multidisciplinary efforts are critical to making HR testing a more consistent part of routine care.