Liquid Biopsy for Patients With Prostate Cancer May Determine Drug Treatment Response
A recent study suggests that a liquid biopsy may help oncologists to determine which patients with prostate cancer are likely to respond to enzalutamide or abiraterone.
A study published in the Annals of Oncology used liquid biopsies from patients with castration-resistant prostate cancer to show that copy number gain of the androgen receptor gene (AR gain) or mutations in AR gene were associated with worse clinical outcomes with enzalutamide or abiraterone, which are the standard therapies targeting testosterone synthesis.1
“Our results show that the detection of AR CN [copy number] gain before starting enzalutamide or abiraterone is associated with decreased OS [overall survival] and PFS [progression-free survival] regardless of prior chemotherapy status,” the study authors wrote.
The researchers used a droplet digital polymerase chain reaction assay that can be widely used on plasma DNA in clinical laboratories. The method is relatively inexpensive, costing about $65.
“Testing plasma AR status by ddPCR is affordable and can be widely implemented in clinical laboratories, but does not control for plasma DNA tumor content that may introduce a bias,” the study authors contend.
Earlier studies provided similar insights using next-generation sequencing.2-5
“This is an emerging field in the treatment of prostate cancer,” prostate cancer expert Anthony V. D'Amico, MD, PhD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, told Cancer Therapy Advisor.
Dr D'Amico noted that researchers at the Johns Hopkins University School of Medicine reported similar results regarding mutations in the AR splice variant 7 (AR-V7) and response to abiraterone and enzalutamide.6 In the present study, however, the AR gene status was determined from circulating tumor cells.
Two cohorts were used for this study: the primary cohort of 171 men was treated with enzalutamide or abiraterone — 73 men received this treatment before docetaxel and 98 after. The second cohort included 94 men from the PREMIERE (ClinicalTrials.gov Identifier: NCT02288936) study.
Peripheral blood was collected from patients before treatment and again after disease progression.
The researchers used DNA from peripheral blood and analyzed the samples for AR gain and for point mutations in the AR gene (2105T>A, 2632A>G, and 2629T>C).
In the primary cohort, OS analysis based on AR status showed a significant association between AR gene status and OS in both chemotherapy-naïve patients and those who previously received docetaxel.