Howard I. Scher, MD
In a study reported in JAMA Oncology, Howard I. Scher, MD, of the Genitourinary Oncology Service, Memorial Sloan Kettering Cancer, and colleagues found that the presence of nuclear-localized androgen receptor splice variant 7 (AR-V7) protein in circulating tumor cells may predict better survival with taxane therapy vs androgen receptor signaling inhibitor treatment in metastatic castration-resistant prostate cancer.
This blinded correlative study included the use of a validated assay for AR-V7 in 142 patients treated at Memorial Sloan Kettering Cancer Center, The Royal Marsden, or the London Health Sciences Centre. Blood samples were obtained prior to the start of androgen receptor signaling inhibitors (n = 70) or taxanes (n = 72) as second-line or greater treatment for progressive disease. The outcome of interest was overall survival after treatment with an androgen receptor signaling inhibitor or taxane in relation to pretherapy AR-V7 status. More patients received taxanes in later than second-line treatment.
Median overall survival among all patients was 16 months among patients receiving ARS inhibitors vs 12.9 months among those receiving taxanes (P = .18). Circulating tumor cells were AR-V7–positive in 14 of 70 patients receiving an androgen receptor signaling inhibitor and 22 of 72 receiving a taxane. Median overall survival was 19.8 months vs 12.8 months among AR-V7–negative patients (hazard ratio [HR] = 1.67, P = .05) and 7.3 months vs 14.3 months among AR-V7–positive patients (HR = 0.62, P = .25). Among 70 patients considered as higher risk on the basis of conventional prognostic factors, the median overall survival was 16.9 vs 9.7 months for AR-V7–negative patients (HR = 2.38, P = .02) and 5.6 vs 14.3 months for AR-V7–positive patients (HR = 0.35, P = .03).
The investigators concluded, “This study suggests that nuclear-localized AR-V7 protein in circulating tumor cells can identify patients who may live longer with taxane chemotherapy vs [androgen receptor signaling] inhibitor treatment.” ■