AR-V7 CTC test informs treatment decision-making in metastatic prostate cancer

Determining the presence of androgen receptor splice variant 7 (AR-V7) protein in circulating tumour cells (CTC) improves the clinical decision-making process when choosing between an androgen receptor signalling inhibitor (ARSI) or a taxane at the start of second or greater line of therapy in men with progressing metastatic castration-resistant prostate cancer (mCRPC), a study has shown.

“The results of our analysis suggest that AR-V7–positive patients would experience better survival on taxanes over ARSIs, and AR-V7–negative patients would have superior survival if given an ARSI. However, the latter finding is less clear-cut and thus individual patient assignment in the AR-V7–negative setting should still be guided by best physician judgment,” the investigators said.

The clinical utility of the AR-V7 in CTCs as a biomarker has been previously established, informing treatment decisions and improving patient outcomes relative to when it is not used. The investigators used these data to examine the drivers of treatment choice when AR-V7 status was unknown and how the knowledge of such status affected survival. [JAMA Oncol 2016;2:1441-1449; JAMA Oncol 2018;4:1179-1186]

A total 255 CTC samples tested for AR-V7 from 193 unique patients with progressing mCRPC were included in the analysis. Samples were drawn at the time of the second or later line treatment decision, with up to 3 year of additional follow-up.

Results revealed that treating physicians were more likely to choose a taxane over an ARSI for patients with more advanced disease or who received an ARSI as the immediate prior therapy. In an analysis controlling for physician propensity, overall survival (OS) did not significantly differ between taxane- and ARSI-treated patients (median, 15.6 vs 14.4 months; p=0.11). [Eur Urol 2019;doi:10.1016/j.eururo.2019.08.020]

“In practice, there is physician bias against prescribing ARSIs sequentially because of presumed cross-resistance in individual patients,” the investigators pointed out.

However, OS was not correlated with the interaction between prior therapy and next therapy chosen (hazard ratio, 0.61, 95 percent confidence interval, 0.29–1.3; p=0.55).

The above, combined with the similar survival outcomes with the two drug classes, with 66 percent of patients having received an ARSI as their immediate prior therapy, “argues against the assumption that there can be no benefit from sequential ARSI use,” they said.

Meanwhile, in the subgroup of patients with detectable nuclear-localized AR-V7 in CTCs, OS was markedly longer with taxanes vs ARSIs (median, 9.8 vs 5.7 months; p=0.041). Conversely, AR-V7–negative patients had better OS on ARSIs (p=0.033), although the investigators noted overlapping curves, which limited the interpretation.

“Taken together, the study results show that knowledge of AR-V7 status before making a treatment decision for mCRPC in the second line or greater might provide incremental value that could result in better survival for patients in need of a new line of therapy,” the investigators said.

“Additional biomarkers are still needed to understand why some AR-V7–negative patients do not respond to an ARSI and to identify them a priori so that alternative, potentially effective treatments can be given,” they continued. “However, the incremental value to clinical decision-making will also need to be demonstrated for any such additional biomarkers.”