TOPLINE:
A minority of patients with metastatic castration-resistant prostate cancer (mCRPC) in the United States undergo genetic testing for homologous recombination repair (HRR) mutations, despite the potential prognostic and predictive value of these mutations for therapies like poly(ADP-ribose) polymerase (PARP) inhibitors, research shows.
METHODOLOGY:
- HRR gene mutations are found in approximately 25%-30% of patients with mCRPC. Genetic testing can inform treatment decisions, such as the use of PARP inhibitors, and was recommended in national guidelines in 2018. Yet, data on testing rates are lacking.
- Using the Flatiron Health electronic health record database, researchers identified 9395 men treated for mCRPC between 2014 and 2022.
- The authors assessed the use of HRR mutation genetic testing, including next-generation sequencing — specifically any somatic HRR, tissue, or circulating tumor DNA test — or a somatic or germline BRCA test.
- The researchers then determined the timing of HRR testing relative to mCRPC diagnosis and initiation of first-line therapy and identified factors associated with HRR testing.
TAKEAWAY:
- Overall, 37.7% of patients (3538 of 9395 patients) received HRR testing; the majority (62.3%) did not. The proportion of patients tested peaked in 2020 at 55.5%, with a small decline in testing rates after 2020, possibly due to the COVID-19 pandemic.
- From 2014 to 2019, 74% of patients who received HRR testing (1546 of 2090) and 23% of all patients (1546 of 6688) underwent the test more than 12 weeks after initiating first-line therapy.
- In 2020, the timing of testing started to improve. By 2022, 92% (304 of 327) HRR-tested patients and 46% (304 of 662) of all patients received the test within 12 weeks of initiating first-line therapy.
- Factors associated with lower odds of HRR testing included being diagnosed before 2018 (odds ratio [OR], 0.30), no prior treatment for localized disease (OR, 0.64), Eastern Cooperative Oncology Group performance status of 1 (OR, 0.78) or 2+ (OR, 0.52) and de novo disease (OR, 0.65). Lower socioeconomic status, Medicaid insurance, treatment outside academic centers, and older age were associated with lower odds of testing.
IN PRACTICE:
"These findings highlight disparities in receiving HRR testing in the US," the authors wrote. "While the use of genomic-based therapies was not the focus of this study, the low testing rates observed in our cross-sectional study would be further compounded by low utilization of targeted therapies among patients who are known to be eligible."
SOURCE:
The study, with first author Pedro C. Barata, MD, MSc, University Hospitals Seidman Cancer Center, Cleveland, was published online on May 2 in JAMA Oncology.
LIMITATIONS:
The study had incomplete information on the type of genetic testing and the number of genes included in each test. Most patients were from a community setting, so testing rates may not reflect rates in academic centers.
DISCLOSURES:
The study was funded by Pfizer Inc. Three authors disclosed relationships with the company.
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