Genomics

Multi-Institutional Evaluation of the Clinical Outcomes and Genomic Correlates of African Americans with Metastatic Castration-Sensitive Prostate Cancer


(UroToday.com) It remains that African American (AA) men experience higher rates of incidence of prostate cancer and prostate cancer-specific mortality than do their non-AA counterparts. Multifaceted efforts are underway at several centers to isolate and address the biological and non-biological contributors to these fundamental health disparities. Among a gap between AA and non-AA prostate cancer patients is the rates of clinical trial enrollment.1 As advanced therapies have improved the outcomes for patients with metastatic castration-sensitive prostate cancer (mCSPC), the trials demonstrating these benefits have continued to underrepresent the AA community. In the absence of prospective data, Dr. Freeman and colleagues used retrospective data from six academic cancer centers to describe the clinical and genomic landscape of AA mCSPC.

The collection of data across these sites yield a total of 71 AA subjects with mCSPC. Their baseline demographics included a median age of 63 years (range 41-84), high rates of Gleason grade 8-10 (58%), and de novo metastases (59%). More than half (55%) had high-volume disease by CHAARTED criteria, among which 20% had visceral disease. Initial treatment data reflected historical trends, with 22 (31%) of subjects receiving androgen deprivation therapy (ADT) monotherapy (15 of these 22 were prior to 2017). Abiraterone acetate plus prednisone and enzalutamide were used in 24% and 45% of men, respectively. Only 3% of subjects received docetaxel therapy at a median cycle number of six. Two patients received “triplet” therapy, combing docetaxel with either abiraterone or enzalutamide.

Thirty-five percent of patients developed an undetectable prostate-specific antigen (PSA) (after a median of 8.9 months, range 1.8-22.3) and castration resistance was manifested in 32 patients at an estimated median time of 2.9 years (95% confidence interval [CI], 1.6-4.2). Subsequent therapies included the expected variety of agents, with abiraterone acetate being the most common (41%). The germline of ficve patients (8%) contained known pathogenic alterations, including in BRCA1 (n = 2), HOXB13, PALB2, and PMS2 (all n =1). Assessment of somatic alterations from a subset of the cohort (27 patients) revealed recurrent alterations in CDK12, SPOP, TP53, and TMPRSS2-ERG (fusions), each of 11% (3/27) frequency. Of note, this frequency of TMPRSS2-ERG fusions is lower than what is commonly reported in non-AA populations, and in general, trend with what is reported in AA cohorts.2,3

Freeman et al. provide an assessment of the disease characteristics of AA men with mCSPC, the therapies received, and their outcomes, across six US centers. These data, as retrospectively collected, suggest the possibility of higher rates of both high-volume and de novo metastatic disease in AA men, conclusions that warrant larger investigations to confirm these patterns and isolate their social or biologic causes. Again, as observed in the overall mCSPC community, independent of ancestry, rates of ADT alone in mCSPC remain rather high. The authors note the robust rate of deep PSA response in this AA cohort, which is similar to retrospect case-cohort data suggesting better initial PSA response in AA men exposed to abiraterone acetate.4 The molecular mechanisms for this require further focused and prospective investigations to determine whether these data should influence the selection of an initial agent to add to ADT in AA men with mCSPC.

Presented by: Meredith Freeman, BS, Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana

Written by: Jones Nauseef, MD, PhD, Fellow, Division of Hematology and Oncology, Weill Cornell Medicine/New York Presbyterian Hospital, New York, New York, Twitter: @DrJonesNauseef during the 2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021

References:

1. Spratt, Daniel E., and Joseph R. Osborne. “Disparities in castration-resistant prostate cancer trials.” Journal of Clinical Oncology 33, no. 10 (2015): 1101.

2. Khani, Francesca, Juan Miguel Mosquera, Kyung Park, Mirjam Blattner, Catherine O’Reilly, Theresa Y. MacDonald, Zhengming Chen et al. “Evidence for molecular differences in prostate cancer between African American and Caucasian men.” Clinical Cancer Research 20, no. 18 (2014): 4925-4934.

3. Koga, Yusuke, Hanbing Song, Zachary R. Chalmers, Justin Newberg, Eejung Kim, Jian Carrot-Zhang, Daphnee Piou et al. “Genomic profiling of prostate cancers from men with African and European ancestry.” Clinical Cancer Research 26, no. 17 (2020): 4651-4660.

4. Ramalingam, Sundhar, Michael S. Humeniuk, Rachel Hu, Julia Rasmussen, Patrick Healy, Yuan Wu, Michael R. Harrison, Andrew J. Armstrong, Daniel J. George, and Tian Zhang. “Prostate-specific antigen response in black and white patients treated with abiraterone acetate for metastatic castrate–resistant prostate cancer.” In Urologic Oncology: Seminars and Original Investigations, vol. 35, no. 6, pp. 418-424. Elsevier, 2017.



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