Key Takeaways:

• An analysis of real-world data shows that most patients with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (MCRPC) were treated with an androgen receptor pathway inhibitor (ARPI) prior to receiving the talazoparib plus enzalutamide therapy.
• The most common HRR mutations observed in patients were BRCA2, CDK12, and ATM, highlighting the importance of broad HRR mutation testing in developing treatment plans and oncology pathways.
• Further research focused on patient characteristics and prior treatment is needed to determine the real-world efficacy of talazoparib plus enzalutamide for patients with MCRPC.

In this interview, Andy Osterland, PharmD, MS, a research scientist at Ontada, discusses findings from the study, “Real-World Characteristics and Treatment Patterns of Patients Treated with Talazoparib + Enzalutamide for Metastatic Castration-Resistant Prostate Cancer in the US Community Oncology Setting.” The study examined the characteristics and treatment history of patients initiating treatment with talazoparib plus enzalutamide in order to inform future evaluations of the treatment’s real-world efficacy. Osterland explains how the study’s findings could inform the development of treatment plans for patients with MCRPC as well as HRR mutation testing.

Andy Osterland, PharmD, MS: My name is Andy Osterland. I’m a research scientist with Ontada, and I conduct real-world evidence studies from a US community oncology perspective. I’m also a trained pharmacist, and I completed a fellowship in health economics and outcomes research.

Can you briefly summarize this study and the key findings clinicians should take away from it?

Dr Osterland: We conducted a retrospective real-world analysis using both structured and unstructured electronic health record (EHR) data from a large community oncology network. We identified 52 patients who initiated talazoparib plus enzalutamide between its US Food and Drug Administration (FDA) approval in June 2023 for the treatment of adult patients with HRR gene-mutated MCRPC. We followed patients all the way through December 2024.

This study provides early evidence describing real-world patient characteristics and the use of talazoparib plus enzalutamide for MCRPC in this setting, including some of the most common high-resolution manometry (HRM), which were BRCA2, CDK12, and ATM. We also observed that most patients had high-volume disease and prior treatment with androgen receptor pathway inhibitors (ARPIs), most of whom would not have met some of the strict trial eligibility criteria. The results from the study helped provide context and set expectations for real-world effectiveness of this regimen while also complementing the clinical trial data with subgroups that were previously underrepresented.

How are oncologists deciding where talazoparib plus enzalutamide fits in the treatment sequence for MCRPC patients who have already received prior ARPI therapy?

Dr Osterland: We did see some variability in treatment sequencing, with 44 patients having prior treatment with an ARPI, which was 85% of our cohort. Now, of the 44 patients with prior ARPI, 75% initiated ARPI prior to documentation of castration resistance, whereas 25% initiated ARPI after documentation of castration resistance. These patients would likely have been excluded from the clinical trial. This likely reflects the complexity of real-world decision-making for new approved treatments.

What do these real-world findings tell us about which MCRPC patients are most likely to receive talazoparib plus enzalutamide in community practice?

Dr Osterland: As expected, real-world patients represent a more diverse population than those enrolled in clinical trials. There was also a small proportion of patients with poor performance status who are typically excluded from trials. We saw a relatively high metastasis burden in patients with prior treatment with ARPI. These differences will be important to recognize in future studies of real-world effectiveness.

How has the approval of talazoparib plus enzalutamide changed the role of HRR mutation testing in clinical pathways for prostate cancer?

Dr Osterland: The approval has reinforced HRR mutation testing to help inform treatment selection, and the use of broader HRR gene panels inclusive of non-BRCA HRR mutations is important to consider rather than approaches that are limited to only testing BRCA gene mutations.

How are clinicians approaching treatment decisions for patients with non-BRCA HRR mutations such as CDK12 or ATM?

Dr Osterland: Within our study, the most common HRR mutations we observed were BRCA2, CDK12, and ATM, which were directionally consistent with the clinical trial. Importantly, over a third of the cohort had a non-BRCA HRR mutation and no BRCA mutation. This emphasizes the importance of comprehensive HRR gene panels to help identify these actionable non-BRCA HRR mutations that might be missed following a BRCA-only testing approach.

What additional real-world evidence would be most valuable for helping oncology pathways programs determine the best use of telazopramib plus enzalutamide?

Dr Osterland: Additional data is needed to understand the effectiveness of this regimen in real-world clinical practice. That will complement the safety and efficacy that was demonstrated in the clinical trial. Based on the findings of this study, it will be important to consider the differences in patient characteristics and prior treatment history when interpreting future analyses of real-world effectiveness.