AR-V7 status could inform treatment choice in mCRPC
medwireNews: Researchers have used a protein-based assay to confirm the validity of nuclear-localized androgen receptor splice variant 7 (AR-V7) protein as a predictor of response to therapy for metastatic castration-resistant prostate cancer (mCRPC).
Howard Scher (Memorial Sloan Kettering Cancer Center, New York, USA) and team found that patients with AR-V7–negative circulating tumor cells prior to second- or later-line systemic therapy survived longer when treated with androgen receptor signaling (ARS) inhibitors than when treated with taxanes, whereas the reverse was true for patients with AR-V7–positive circulating tumor cells.
Among the 142 men (mean age 69.5 years) included in the correlative study, 70 were treated with an ARS inhibitor, and 72 received a taxane. ARS inhibitors were mostly used as a second-line treatment whereas taxanes were more common in later lines of therapy.
The researchers report in JAMA Oncology that median overall survival (OS) was a significant 67% longer in patients negative for AR-V7 who were treated with ARS inhibitors (n=56) than in those treated with taxanes (n=52), at 19.8 vs 12.8 months.
By contrast, patients positive for AR-V7 who were treated with ARS inhibitors (n=14) had shorter survival than those treated with taxanes (n=20), at a median 7.3 vs 14.3 months. This difference was not statistically significant, possibly due to the small sample size, Scher et al note.
However, when the investigators focused on 70 patients classed as high risk by clinical prognostic factors, they found that the differential effect of treatment according to AR-V7 status was significant for both AR-V7–negative and positive patients.
Specifically, median OS was 16.9 versus 9.7 months (hazard ratio [HR]=2.38) among AR-V7–negative patients treated with ARS inhibitors versus taxanes, and 5.6 versus 14.3 months (HR=0.35), respectively among AR-V7–positive patients.
For the study, Scher and co-investigators used a protein-based assay that they developed to enable them to determine whether AR-V7 was located in the nucleus of the circulating tumor cells, something that cannot be done when detecting mRNA.
They conclude: “The study results validate the clinical utility of the Epic Sciences nuclear-localized AR-V7 assay to inform the choice between ARS inhibitors or taxanes for patients with mCRPC who are in need of a treatment change in the second-line or greater therapy setting.”
In an accompanying comment, Stephen Plymate, from the University of Washington in Seattle, USA, and co-authors say that if these findings are confirmed, “data on AR-V7 could affect survival and quality of life and substantially decrease the high costs of therapy.”
However, they caution that there is a need to determine whether the protein assay is prognostic or predictive. “Studies must correlate response to treatment with assay positivity, and not just survival data, to ensure that the assay is not simply a prognostic biomarker,” Plymate et al conclude.
By Laura Cowen
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