ASCO 2022: Biomarker-Directed Therapy in Black and White Men With Metastatic Castration-Resistant Prostate Cancer

( At the 2022 American Society of Clinical Oncology Annual Meeting held in Chicago and virtually, the poster session focused on Prostate, Testicular, and Penile cancers on Monday afternoon included a presentation from Dr. Clara Hwang presenting an analysis of biomarker-directed therapy in men with metastatic castration-resistant prostate cancer (mCRPC).

Despite identified worse outcomes (higher incidence and mortality) in Black men with prostate cancer, Black men have been underrepresented in large-scale molecular prostate cancer surveys. Given that molecular profiling to guide the use of targeted agents is gaining an increasingly important role in mCRPC, these authors compared precision medicine data and utilization in a cohort of black and white men with mCRPC.

To do so, they leveraged the PROMISE precision medicine database, an academic collaboration to compile clinical and genomic data from men with prostate cancer. In this dataset, all included patients have had germline or somatic genetic testing performed.

In this analysis, the authors included men with a diagnosis of mCRPC who had available data on race and biomarker information. The primary outcome was the proportion of non-Hispanic black (NHB) and non-Hispanic white (NHW) men with actionable molecular data, defined as the presence of mismatch repair deficiency (MMRd/MSI-H), homologous recombination repair deficiency (HRRd), tumor mutational burden (TMB) ≥ 10 mut/MB, or AR-V7. In addition, the authors assessed secondary outcomes including the proportion of NHB and NHW men with other alterations, the type and timing of genomic testing performed, and the use of targeted therapy.

Among 1619 men in the overall dataset, 962 mCRPC patients met inclusion criteria of whom 21.2% were non-Hispanic black and 78.8% were non-Hispanic white. There were some differences at baseline on the basis of race: of non-Hispanic black men we somewhat younger (61 vs 63 years) and were more likely to have high grade (Gleason score 8-10) histology (77.5 vs 68.8%). However, of non-Hispanic white men were somewhat more likely (56.7 vs 52.5%) to have presented with de novo metastatic disease.

ASCO22_Clara Hwang_0 

The median time from diagnosis to first molecular result was 56.3 months for non-Hispanic black men compared to 58.7 months for non-Hispanic white men (p = 0.45). Further, use of blood-based molecular testing was more common in non-Hispanic black men (48.7% v 36.4%, p < 0.001).

Overall, actionable molecular alterations were found in 32.8% of non-Hispanic black men as compared with 30.3% of non-Hispanic white men. In particular, MMRd/MSI-H was more common in non-Hispanic black men (9.1 v 4.9%, p = 0.04) as were PTEN alterations (12.7/23.8%, p = 0.0001). However, there were no significant differences seen in the 15 most frequently mutated genes, including TP53, AR, CDK12, RB1, and PIK3CA.

ASCO22_Clara Hwang_1 

Tumor suppressor co-mutations (PTEN/TP53/RB1) were found in 13.1% of non-Hispanic black and 18.0% non-Hispanic white men (p = 0.13). Delivery of targeted therapy was reported in 19.6% of non-Hispanic black and 23.7% of non-Hispanic white men (p = 0.25) after a median of 2 lines of treatment for CRPC. Median OS from development of mCRPC was 41.5 months (95% CI, 34.7-51.3) for non-Hispanic black and 44.7 months (95% CI, 41.1-51.5) for non-Hispanic white men, respectively (p = 0.14).

ASCO22_Clara Hwang_2 

Thus, the authors conclude that, in a real-world mCRPC molecular profiling cohort, there are similar overall rates of actionable molecular alterations in non-Hispanic black and non-Hispanic white men, but higher rates of MMRd/MSI-H and lower frequency of PTEN alterations in non-Hispanic black men. Further, there was not evidence of differences in the delivery of targeted therapy.

Presented by: Clara Hwang, MD, Henry Ford Health System, Detroit, MI

Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022.


email news signup