The promise of precision oncology depends not only on scientific innovation but also on successful implementation in routine clinical practice. Drawing on real-world data from community oncology settings, Andrew Osterland, PharmD, MS, Research Scientist at Ontada, shares insights into the use of talazoparib plus enzalutamide for metastatic castration-resistant prostate cancer and the evolving landscape of HRR testing.

His findings reveal both encouraging progress and important opportunities to improve access to personalized treatment approaches.

Q: What emerging treatment trends are you observing among patients receiving talazoparib plus enzalutamide (T+E) for metastatic castration-resistant prostate cancer? 

• A: We conducted a retrospective real-world analysis using both structured and unstructured EHR data from a large community oncology network. We identified 52 patients who initiated T+E between its FDA approval for prostate cancer in June of 2023 through December of 2024. As expected, real-world patients represented 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 also saw a relatively high metastasis burden in patients with prior ARPi, most of whom would not have met the strict trial eligibility criteria. These differences will be important to recognize in future studies that evaluate real-world effectiveness of this combination regimen. 
• Additionally, the most common HRR mutations we observed were in the BRCA2, CDK12, ATM, and CHEK2 genes, which was relatively consistent with the clinical trial. At the same time, we did observe some variability in HRR testing patterns and documentation of results, which highlights an ongoing gap between clinical trial protocols and real-world practice patterns. 

How closely do real-world treatment patterns align with outcomes observed in clinical trials for these therapies?

• A: Among eligible patients, we observed that T+E is being adopted in the community setting, largely in line with its approved indication in patients with HRR-mutated metastatic castration-resistant prostate cancer (mCRPC). We did see some variability in treatment sequencing, with 43% initiating after one or more treatments in the mCRPC setting, and 85% of patients having prior treatment with an ARPi, which likely reflects the complexity of real-world decision-making for newly approved treatments. 

Your research also explores HRR testing in metastatic castration-sensitive prostate cancer. Why is broader adoption of genomic testing becoming increasingly important?

A: Earlier testing aligns with current NCCN guidelines, which recommend testing for HRR mutations in all patients with metastatic prostate cancer, along with patients with high- or very high-risk localized or regional disease. Additionally, patients with a family history of certain cancers, including prostate cancer, or a familial cancer risk mutation are recommended to receive testing. This ensures that providers have information they need to make timely, informed treatment decisions, particularly around the use of targeted therapies and eligibility for clinical trials. 

What disparities or gaps still exist in access to biomarker and HRR testing within community oncology settings? 

• A: There are several barriers that continue to limit the broader adoption of HRR testing. Previous studies of HRR testing in the mCRPC setting found that testing is more likely among patients with high-risk clinical features, such as family history of prostate cancer or a Gleason score of eight or more and then less likely among older patients, those with poor performance status, or those facing socioeconomic barriers, such as insurance type and income. In our analysis, we observed some similar themes. Patients with more advanced disease, such as metastatic disease and higher PSA levels, were more likely to undergo testing, while lower testing rates were seen among patients 70 years of age or older. 
• Addressing these gaps will require more standardized and proactive approaches such as reflex testing at the time of metastatic diagnosis, along with increased education and improved care coordination. These types of multi-disciplinary efforts are critical to making HRR testing a more consistent, routine part of care. 

How do you expect precision oncology approaches in prostate cancer to evolve over the next several years? 

• A: As we learn more about clinical outcomes by HRR mutation status, particularly in earlier settings like metastatic castration-sensitive prostate cancer, this will not only help inform risk stratification but also identify areas for unmet need within the mCRPC setting where the safety and efficacy of targeted therapies can be assessed through clinical trials. 

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