In yesterday’s post I wrote about the possibility of looking for the presence of the splice variant ARV7 to determine if you would be resistant to enzalutamide (Xtandi). Today I am going to expand on this issue and discuss an additional study that demonstrated that the presence of ARV7 in circulating tumor cells not only can predict initial resistance to Xtandi, but it also can predict resistance to abiraterone (Zytiga).
For the technical among us androgen receptor splice variant-7 (ARV7) is a truncated form of the androgen receptor that lacks the ligand-binding domain, the target of enzalutamide and abiraterone, but remains constitutively active as a transcription factor.
Now to the bottom line findings without technical jargon- This study evaluated 31men treated with Xtandi and 31 treated with Zytiga. Of the men treated with Xtandi, 38.7% had detectable ARV7 and in the Zytiga group 19.4% had detectable ARV7.
Among men receiving enzalutamide, AR-V7–positive men had inferior PSA response rates (0% vs 52.6%, P=0.004), PSA-PFS (median 1.4 vs 5.9 months, P<0.001), and PFS (median 2.1 vs 6.1 months, P<0.001) compared to AR-V7–negative men.
Similarly, among men receiving abiraterone, ARV7 positive men had inferior PSA response rates (0% vs 68.0%, P=0.004), PSA-PFS (median 1.3 months vs not reached, P<0.001), and PFS (median 2.3 months vs not reached, P<0.001).
CONCLUSION- The detection of ARV7 in circulating tumor cells in men with mCRPC is associated with resistance to both enzalutamide and abiraterone. We should ask our doctors to consider our ARV7 status as a potential biomarker to predict our resistance to AR-targeting agents like Xtandi and Zytiga to facilitate our treatment selection. Yesterday’s study along with this one should fuel the development AR N-terminal domain inhibitors to short circuit this issue.
J Clin Oncol 32:5s, 2014 (suppl; abstr 5001); Emmanuel S. Antonarakis, Changxue Lu, Hao Wang, Brandon Luber, Mary Nakazawa, Yan Chen, Jeffrey C. Roeser, Helen L. Fedor, Tamara L. Lotan, Qizhi Zheng, Angelo M. De Marzo, John T. Isaacs, William B. Isaacs, Rosa Nadal, Channing Judith Paller, Samuel R. Denmeade, Michael Anthony Carducci, Mario A. Eisenberger, Jun Luo
Joel T. Nowak, M.A., M.S.W.