Study reinforces value of precision medicine in prostate cancer

Data presented at the 2024 ASCO Annual Meeting showed racial differences in the frequency of genomic alterations in immunotherapy targets among patients with metastatic prostate cancer from the Veterans Affairs Healthcare System, supporting the use of next-generation sequencing to identify patients for precision oncology treatments.¹

Consistent with prior work, a significantly higher risk of PCSM was observed among both non-Hispanic Black and non-Hispanic White patients who had alterations in TP53 and tumor suppressor pathways.

The findings were presented by lead author Luca F. Valle, MD, an assistant professor of radiation oncology at the David Geffen School of Medicine at the University of California, Los Angeles.

“One of the highlights of our analysis is the prevalence of clinically actionable alterations that are affecting a significant proportion of individuals, regardless of race,” said Valle in a news release on the findings.² “This means we may be able to use specific medications that target vulnerabilities in tumors associated with the genomic changes we observed. Ensuring equal access to genomic tumor testing and precision medicine treatments may be a viable strategy to help close the well-described gaps in prostate cancer outcomes between Black and White men. This work really emphasizes the fact that equal access healthcare systems, such as the Veterans Affairs Healthcare System, enable precision-guided therapies, which may result in more equitable outcomes in men with advanced prostate cancer.”

Overall, data from next-generation sequencing of primary tumors and metastatic tissues showed a similar spectrum of altered genes among all patients in the study but demonstrated different frequencies of alterations between non-Hispanic Black and non-Hispanic White men.

Significantly higher frequencies of genomic alterations in immunotherapy targets, SPOP, and BRAF (all P < .05), were seen among patients with non-Hispanic Black race/ethnicity. Specifically, the rate of genomic alterations in immunotherapy targets was 9.2% among non-Hispanic Black patients vs 6.1% among non-Hispanic White patients (P < .01).

Non-Hispanic Black race/ethnicity was also associated with lower rates of genomic alterations in the AKT/PI3K pathway, AR axis, and tumor suppressor genes, including TP53 and PTEN, compared with non-Hispanic White race/ethnicity (all P < .05).

Consistent with prior work, a significantly higher risk of prostate cancer–specific mortality (PCSM) was observed among both non-Hispanic Black and non-Hispanic White patients who had alterations in TP53 (HR, 1.5; 95% CI, 1.1-2.0; P = .007) and tumor suppressor pathways (HR, 1.3; 95% CI, 1.0-1.8; P = .04).However, race was not shown to be independently associated with PCSM.

In total, the study included 5015 patients with metastatic prostate cancer, of which 36% (n = 1784) self-identified as non-Hispanic Black and 64% (n = 3231) self-identified as non-Hispanic White. Compared with the non-Hispanic White patients, non-Hispanic Black patients tended to be younger at diagnosis, have significantly higher PSAs at diagnosis, and were less likely to report Agent Orange exposure and more likely to reside in neighborhoods with higher area deprivation index.

Next-generation sequencing was conducted on primary tumors in 47.0% of (n = 2359) patients, metastases in 20.2% (n = 1011) of patients, and cell-free DNA (liquid biopsies) in 32.8% (n = 1645) of patients.

Valle concluded in the news release, “Overall, this study really reinforces the importance of precision medicine initiatives for men with advanced prostate cancer. By integrating tumor genomic information into patient selection for metastatic prostate cancer treatments or clinical trials, healthcare providers can strive to improve treatment outcomes for all patients, irrespective of race or ethnicity.”²

References

1. Valle LF, Li J, Desai H, et al. Oncogenic alteration rates, race, and prostate cancer specific mortality in Veterans with metastatic prostate cancer undergoing somatic tumor next generation sequencing. Presented at: 2024 American Society for Clinical Oncology Annual Meeting. May 31-June 4, Chicago, Illinois. Abstract 5017. https://ascopubs.org/doi/abs/10.1200/JCO.2024.42.16_suppl.5017

2. ASCO: Large precision oncology study identifies differences in prostate cancer genomics among a racially and ethnically diverse cohort of U.S. veterans. News release. University of California, Los Angeles (UCLA), Health Sciences. May 24, 2024. Accessed June 5, 2024. https://www.newswise.com/articles/asco-large-precision-oncology-study-identifies-differences-in-prostate-cancer-genomics-among-a-racially-and-ethnically-diverse-cohort-of-u-s-veterans