AR-V7 status not associated with taxane chemotherapy resistance in advanced prostate cancer
Men with metastatic castration-resistant prostate cancer demonstrated similar responses to taxane chemotherapy regardless of whether they had androgen receptor V7-positive disease, according to study results presented at the Genitourinary Cancers Symposium.
Emmanuel S. Antonarakis, MBBCh, assistant professor of oncology and urology at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, and colleagues previously demonstrated that the presence of androgen receptor V7 (AR-V7) — a truncated form of the androgen receptor — in circulating tumor cells (CTCs) was associated with resistance to hormone therapy with enzalutamide (Xtandi; Astellas, Medivation) and abiraterone acetate (Zytiga, Janssen). The researchers sought to determine whether AR-V7 in CTCs also was associated with resistance to taxane chemotherapy.
Emmanuel S. Antonarakis
Their analysis included 37 patients with metastatic castration-resistant prostate cancer who started treatment with docetaxel or cabazitaxel (Jevtana, Sanofi-Aventis).
Researchers detected AR-V7 in the CTCs of 17 (45.9%) of the men.
A PSA response to taxane chemotherapy — which served as the study’s primary endpoint — occurred in 41% of men with AR-V7–positive disease and 65% of those with AR-V7–negative disease. The difference was not statistically significant.
Researchers observed no statistically significant differences between men with AR-V7–positive disease and AR-V7–negative disease with regard to PFS (5.1 months vs. 6.9 months; HR = 2.65) and median PSA PFS (4.5 months vs. 6.2 months; HR = 1.72).
Antonarakis and colleagues then compared these data with results from their previous study on AR-V7, which included 62 men treated with enzalutamide or abiraterone.
Among AR-V7–positive men in both cohorts, a greater proportion of those who received taxane chemotherapy achieved a PSA response (41% vs. 0%; P ˂ .001). Those treated with taxane chemotherapy also demonstrated significantly longer median PSA PFS (HR = 0.19) and median PFS (HR = 0.21) compared with men treated with hormone therapy.
However, responses among men with AR-V7–negative disease were similar with hormone therapy or taxane chemotherapy.
“AR-V7 may potentially serve as a treatment selection marker for men with metastatic castration-resistant prostate cancer seeking therapy with either taxanes or enzalutamide and abiraterone,” Antonarakis said during a press conference. “In my mind, the utility of the test is greater in patients who have a positive result. In those patients, our data suggest taxanes might appear to be quite a bit more efficacious than either enzalutamide or abiraterone.”
Results suggest the two therapeutic approaches could be equally efficacious in AR-V7–negative patients, Antonarakis said.
“Therefore, the utility of a negative test is not so great in my mind as a positive test,” he said. “However, before this data becomes clinically actionable, we need to prospectively validate this finding in at least one multicenter clinical trial.” – by Alexandra Todak
Antonarakis E, et al. Abstract 138. Presented at: Genitourinary Cancers Symposium; Feb. 26-28, 2015; Orlando, Florida.
Disclosure: Antonarakis reports consulting/advisory roles with, honoraria from and research funding from Aragon Pharmaceuticals, Dendreon, Exelixis, Genentech, Janssen, Johnson & Johnson, Medivation, Millennium, Novartis and Sanofi. See the full study for a list of all other researchers’ relevant financial disclosures.