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Sandy Srinivas, MD
Sandy Srinivas, MD
Posted: Tuesday, August 30, 2022
In cases of prostate cancer that become metastatic after the use of standard-of-care hormonal therapies, the prevalence of homologous recombination repair (HRR) gene defects seems to remain stable, according to the results of real-world research published in JCO Precision Oncology. In contrast, biomarkers such as AR and MYC amplifications, or TP53 and RB1 loss, tend to be enriched after resistance to hormone therapy. The data support the use of archival, untreated diagnostic tissue samples for next-generation sequencing testing to identify patients with metastatic castration-resistant prostate cancer who have HRR defects and may benefit from PARP inhibitor therapy, explained Joaquin Mateo, MD, PhD, of Vall d’Hebron Institute of Oncology, Barcelona, and colleagues.
The team used FoundationOne or FoundationOne CDx assays to study targeted next-generation sequencing of 1,302 patients with metastatic prostate cancer, looking particularly at individual gene aberrations and genome-wide loss-of-heterozygosity scores. The investigators compared genomic biomarkers according to both biopsy location and the time of sample acquisition, which was prior to androgen-deprivation therapy (n = 840 patients; 65%), after disease progression on androgen-deprivation therapy (n = 132; 10%), or after disease progression on novel hormonal therapies (n = 330; 25%).
“We observed that genome-wide loss of heterozygosity, a marker of genomic instability, independently associates with the presence of HRR gene alterations, TP53/RB1 loss, and resistance to hormonal therapies,” the study investigators reported. “All patients in our study, including those who were androgen-deprivation therapy–naive at the time of biopsy acquisition, had confirmed progression to late-stage metastatic prostate cancer,” they continued. “Prior comparisons of the genomic landscape studies of primary versus metastatic prostate tumors [might have been] confounded by the inclusion of patients with localized prostate cancer who never developed recurrence.”
Disclosure: The study authors’ disclosure information can be found at ascopubs.org.
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