March 1, 2024

Study sheds light on genetic variations in advanced prostate cancer

Black men with metastatic castration-resistant prostate cancer (mCRPC) had a higher frequency of mismatch repair deficiency (MMRD) or microsatellite instability high (MSI-H) and a lower frequency of PTEN It is TMPRSS changes compared to white men, according to a retrospective cohort study. However, no differences were observed regarding clinical outcomes, even with black men receiving targeted therapy less frequently than white men.

The study included 962 eligible patients with mCRPC, comprising 204 black patients and 758 white patients. We used data collected by the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) consortium from April 2020 to December 2021. Investigators assessed the primary endpoint of frequency of actionable molecular data and secondary endpoints of frequency of other alterations. , the type and timing of genomic testing performed, and the use of targeted therapy.

At a median mCRPC follow-up of 26.6 (14.2-44.7) months, the prevalence of actionable changes was comparable between groups, observed in 65 black men (32.8%) and 215 white men (29 ,1%; P = 0.35). However, MMRD or MSI-H was more prevalent among black men (9.1%) versus white men (4.9%; P = 0.04).

Actionable changes were observed in 65 black patients (32.8%) and 215 white patients (29.1%); P = 0.35), which was comparable. Conversely, MMRD or MSI-H were found to be more common in black men (n = 18; 9.1%) than in white men (n = 36; 4.9%; P = 0.04). PTEN changes occurred less frequently in black men (15.7%) versus white men (26.3%; P = 0.003), as well as TMPRSS changes (7.1% vs 21.0%; P <0.001). No other disparities were observed in the 15 most frequently altered genes, including TP53, AR, CDK12, RB1It is PIK3CA.

The results also showed that blood-based molecular tests were observed more frequently among black men (48.7%) versus white men (36.4%; P <0.001). Additionally, corresponding targeted therapy was administered less frequently to black men compared to white men (33.5% vs 53.5%; P = 0.008). However, no differences in response to targeted therapy or survival were observed between the two cohorts.

In an interview with Targeted OncologyMTClara Hwang, medical oncologist and senior physician at Henry Ford Health, discussed the notable differences in molecular changes observed in the retrospective cohort study among black men with mCRPC compared to white men.

Prostate Cancer, Bladder Cancer, Men’s Health Care: © Tom –

Targeted Oncology: Can you explain the background to this research? How did you arrive at the main question asked in the study?

Hwang: The motivation was the known disparities between black and white men with prostate cancer. We know that black men are more likely to develop prostate cancer and also 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 like to apply precision medicine to prostate cancer, right now, many guidelines recommend genetic testing for patients with advanced prostate cancer. This is because we have targeted therapies that we can offer men with prostate cancer that are beyond standard treatment. For example, we can give pembrolizumab [Keytruda] for patients who have mismatch repair deficiency, we can give [poly-ADP ribose polymerase (PARP)] inhibitors for patients who have BRCA or another [homologous recombination repair (HRR)] defects, and this is beyond your standard of care.

The group I’m working with is called the PROMISE consortium and it’s a clinical genomic database. We captured clinical and genomic information from these patients. We compared the data we had for the black and non-Hispanic white population. We specifically analyzed patients with metastatic castration-resistant prostate cancer. We then specifically compared black versus white patients in this patient population.

What were the methods and designs used?

It was a retrospective chart review. Essentially, it has over 1,500 patients, so it’s a large database run by a consortium. We compared populations based on race and looked at No. 1, whether patients had what we call actionable mutations. Basically, we analyze 3 categories of action of a mutation. As I mentioned, either MSI-H deficiency/mismatch repair would qualify patients to receive pembrolizumab, so this value was 1. We looked at HRR deficiency because this would qualify patients for PARP inhibitors or platinum therapy. We then also looked at TMB status, a high tumor mutational burden, that would qualify patients for pembrolizumab. We saw these 3 categories of action of mutations. We then compared rates in the black and white populations. We also checked whether patients received targeted therapy. We compared other things too, but those were the two main things.

Can you explain the findings that were discovered?

Overall, we found no differences in rates of actionable mutations between black and white men with metastatic prostate cancer. However, what we found was that rates of MSI-H repair deficiency/mismatch were higher in black patients. They were about 5% versus 10% as I recall. Other than that, we saw no significant differences in terms of molecular discoveries.

The other important finding that I would say we reported was the fact that even though black men had higher rates of mismatch repair deficiency, overall, if we look at patients who had actionable mutations, black men were less likely to have receive targeted therapy.

How important is this research and what are the next steps?

First, although we found that there were differences in the administration of precision medicine to black patients, we did not observe differences in survival. We haven’t seen any differences when it comes to cancer outcomes, which I find very reassuring. However, I think it speaks to the fact that there is still room to make progress in terms of ensuring that we have equal or equitable access to care, because I think access to precision medicine is important for all patients with advanced prostate cancer. .

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

When we looked at the data, we knew that some patients, for example, received specific therapies in clinical trials. I think that’s a thing, [we must] ensure we have access to widely available clinical trials. I think this will help a lot. Besides that, [we must] make sure oncologists everywhere are up to date in terms of thinking about targeted therapy for their patients.

For community oncologists, what are the key takeaways from this research?

Number 1, we should definitely be looking for these types of molecular changes and knowing, for example, that black men are more likely to have a molecular change that would make them eligible for pembrolizumab. I think it’s important to remember. We will then look for these mutations early enough in the course of the disease so that we can still offer patients these targeted therapies.

Hwang C, Henderson NC, Chu SC, et al. Biomarker-directed therapy in black and white men with metastatic castration-resistant prostate cancer. Open JAMA Network. 2023;6(9):e2334208. Published September 5, 2023. doi:10.1001/jamanetworkopen.2023.34208

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