Early Genomic Profiling Performed Less in African American Men With Prostate Cancer

Brandon A. Mahal, MD

Disparities in prostate cancer care have been highlighted through a study examining gnomic profiling.

Among the notable findings were that patients with African ancestry are less likely to receive comprehensive genomic profiling earlier in their treatment course, and are also less likely to be treated on clinical trials.

For the study, which was presented at the 2021 ASCO Annual meeting by Brandon A. Mahal, MD, 11,741 patients with prostate cancer with comprehensive genomic profiling done as part of routine care were evaluated, of whom 12% had African ancestry. A single-nucleotide polymorphism-based approach was used to infer predominant ancestry. In addition, the investigators queried a de-identified clinico-genomic database (CGDB) of 897 evaluable patients with prostate cancer to examine trends in comprehensive genomic profiling utilization, treatment patterns, and clinical trial enrollment.

In the larger cohort, the median age was 67 years and 98% had adenocarcinoma histology. The median age of patients with African ancestry was 64 years vs 67 years for patients with European ancestry (P <.001). In addition, 4.2% of patients with African ancestry were younger than 50 years of age vs 2.5% of patients with European ancestry.

Several gene alterations were significantly enriched in patients with African ancestry versus patients with European ancestry in SPOP (11.9% vs 7.3%), CDK12 (10.0% vs 5.2%), CCND1 (6.0% vs 3.8%), KMT2D (7.7% vs 5.1%), HGF (4.1% vs 2.5%), and MYC (13.4% vs 10.6%).

Gene alterations that occurred less frequently in patients with African ancestry versus European ancestry included TP53 (35% vs 43%)and PTEN (21% vs 33%). Additionally, TMPRSS2-ERG rearrangements also occurred less frequently in patients with African ancestry (15% vs 33%).

When comparing targetable gene alterations, the investigators found similar rates of actionable genes (22.1% in patients with African ancestry vs 22.4% in patients with European ancestry) as well as DNA damage response-associated genes (17.8% in patients with African ancestry vs 18.7% in patients with European ancestry). Mahal noted, however, that BRAF alterations were slightly enriched in patients with African ancestry (5.0% vs 3.2%; P <.05).

Turning to the CGDB cohort, Mahal reported that 91% of patients with African ancestry were treated in the community versus 63% of patients with European ancestry.

“Notably, less than 10% of individuals with African ancestry were treated in an academic setting, whereas 37% of individuals with European ancestry were treated in an academic setting,” said Mahal, assistant professor of radiation oncology and assistant director of community outreach and engagement, University of Miami Sylvester Comprehensive Cancer Center, Miami, Florida.

Eighty-five percent of patients with African ancestry had castration-resistant prostate cancer versus 72% of patients with European ancestry.

Also in the CGDB cohort, it was noted that patients with African ancestry received a median of 2 lines of therapy prior to undergoing comprehensive genomic profiling, compared with 1 line of therapy in patients with European ancestry.

“While there were no significant differences in the use of targeted therapies, including PARP inhibitors or other therapies, only 11% of African-ancestry patients received a clinical study drug compared with 30% of European-ancestry patients,” Mahal said. This was observed both for patients treated in the academic setting as well as for patients treated in the community.

“Please note that these findings are from a small cohort, and in particular, in the academic setting, there were only 5 individuals with African ancestry that were treated at academic centers and therefore, these findings must be interpreted within these limitations,” Mahal noted as a caveat.

“Ultimately, equitable use of comprehensive genomic profile testing, clinical trial enrollment, and subsequent precision medicine treatment pathways could lead to a major reduction in disparities,” Mahal concluded.

_Reference

_{Sivakumar S, Lee JK, Moore JA, et al. Ancestral characterization of the genomic landscape, comprehensive genomic profiling utilization, and treatment patterns may inform disparities in advanced prostate cancer: A large-scale analysis. J Clin Oncol 39, 2021 (suppl 15; abstr 5003). doi: 10.1200/JCO.2021.39.15_suppl.5003}