Dr. Clara Hwang discusses study of precision medicine disparities in prostate cancer

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In a recent interview with our sister site TargetedOnc.com, lead study Clara Hwang, MD, author discussed the background and findings from the study, “Biomarker-Directed Therapy in Black and White Men With Metastatic Castration-Resistant Prostate Cancer.”1 Hwang is a medical oncologist and senior staff physician at Henry Ford Health.

Can you explain the background of this research? How did you come up with the main question asked in the study?

Clara Hwang, MD

Clara Hwang, MD

Hwang: The motivation was the known disparities between Black and White men with prostate cancer. We know that Black men are more likely to get prostate cancer and also more than twice as likely to die from prostate cancer. There are multiple reasons for this. What we were looking for in this study was to see if these disparities persisted in the application of precision medicine to prostate cancer.

In terms of why we would want to apply precision medicine for prostate cancer, now, the many guidelines recommend genetic testing for patients with advanced prostate cancer. That is because we have targeted therapies that we can offer to men with prostate cancer that are beyond the standard-of-care. For example, we can give pembrolizumab (Keytruda) to patients who have mismatch repair deficiency, we can PARP inhibitors to patients who have BRCA or other [homologous recombination repair (HRR)] defects, and this is beyond your standard-of-care.

The group that I am working with is called the PROMISE consortium, and it is a clinical genomic database. We capture both clinical and genomic information from these patients. We compared the data that we had for the Black vs the non-Hispanic White population. We looked specifically at patients who have metastatic castration-resistant prostate cancer. Then, we specifically compared Black vs White patients in this patient population.

What were the methods and designs used?

It was a retrospective chart review. Essentially, it has more than 1500 patients, so it is a large, consortium-driven database. We compared the populations based on race, and we looked at number 1, whether patients had what we call actionable mutations. We basically looked at 3 categories of action of a mutation. As I mentioned, both MSI-H/mismatch repair deficiency would qualify for patients for pembrolizumab, so that was one. We looked at HRR deficiency, because that would qualify patients for PARP inhibitors or platinum therapy. Then, we also looked at TMB status, a high tumor mutational burden, which would qualify patients for pembrolizumab. We looked at those 3 categories of action of mutations. Then, we compared rates in the Black vs White population. We also looked to see whether patients received targeted therapy. We compared other things as well, but those were the 2 main things.

Can you elaborate on the findings that were discovered?

Overall, we did not find differences in the rates of actionable mutations between Black and White men with metastatic prostate cancer. However, what we did find was that the rates of MSI-H/mismatch repair deficiency were higher in Black patients. They were about 5% vs 10%, as I recall. Other than that, we did not really see any significant differences in terms of the molecular findings.

The other major finding that I would say that we reported on was the fact that despite Black men having higher rates of mismatch repair deficiency, overall, if we looked at patients who had actionable mutations, Black men were less likely to get targeted therapy.

What is the importance of this research and what are the next steps?

First, even though we saw that there were differences in delivery of precision medicine to Black patients, we did not see differences in survival. We did not see any differences with respect to cancer outcomes, which I think is very reassuring. However, I think it does speak to the fact that there is still room to make progress in terms of making sure we have equal or equitable access to care because I do think that access to precision medicine is important for all patients with advanced prostate cancer.

What are some ways we could improve patients' access to precision medicine?

When we were looking at the data, we did know that some patients did, for example, get targeted therapies on clinical trials. I think that is 1 thing, [we must] make sure we have access to clinical trials widely available. I think that will help a lot. Other than that, [we must] make sure that oncologists everywhere are kept up to date in terms of thinking about targeted therapy for their patients.

Reference
1. Hwang C, Henderson NC, Chu SC, et al. Biomarker-directed therapy in black and white men with metastatic castration-resistant prostate cancer. JAMA Netw Open. 2023;6(9):e2334208. doi: 10.1001/jamanetworkopen.2023.34208

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