AR-V7 Testing in Prostate Cancer - Episode 6
Emmanuel S. Antonarakis, MBBCh: Around 2012, our group began to look at circulating tumor cells from patients with advanced prostate cancer to see whether we could detect the AR-V7—splicing variant and then to determine if it had any prognostic utility in the setting of enzalutamide and abiraterone. So, we initially conducted a small pilot study of 62 patients: 31 of them were receiving enzalutamide for castration-resistant prostate cancer and 31 were receiving abiraterone. We took circulating tumor cells from those patients, and we developed a test that looks for the AR-V7 mRNA in the circulating tumor cells. We asked the question: if the AR-V7 mRNA in the CTCs was present, how does that affect prognosis to enzalutamide and abiraterone? And in that first study, which was published in 2014 in the New England Journal of Medicine, we showed that both in the setting of enzalutamide and in the setting of abiraterone, having AR-V7 mRNA expressed in the circulating tumor cells of these patients was associated, almost in every case, with resistance to both therapies—so a lack of response, a lack of clinical benefit to both therapies.
Now, that study was a small pilot trial for about 62 patients. We have subsequently expanded our study, and we now have data on 202 patients, and this information was recently published in the Journal of Clinical Oncology several weeks ago. And what we showed in that paper is that the negative prognostic value of AR-V7 detection in circulating tumor cells still persists. In other words, the AR-V7—positive patients have inferior outcomes, worst outcomes to enzalutamide and abiraterone, both in terms of progression-free survival and overall survival.
And we did something a little bit different in the expanded analysis. We actually looked at 3 different categories of our biomarker test. The first category was patients who didn’t have any circulating tumor cells detected at all, so we called those patients “CTC-negative.” And then we had a second category where circulating tumor cells were detected in the blood stream, but the AR-V7 was not detected, so we called that category “CTC-positive AR-V7—negative.”
And then we had a third category where not only were CTCs detected in blood, but the AR-V7 mRNA was also detectable. So, we called those “CTC-positive AR-V7—positive.” And it turns out, and it’s perhaps not surprising, that the patients who had no detectable CTCs in their circulation—the CTC-negative patients—had the very best outcomes to both enzalutamide and abiraterone. The patients with CTC-positive AR-V7-positive cases had the worst outcomes, and the patients who had detectable CTCs but without AR-V7—in other words, CTC-positive AR-V7–negative—had intermediate outcomes that were not as bad as the people who had AR-V7–positive cells, but they were not as good as the people who didn’t have any circulating tumor cells whatsoever. So, this was a nice study. It was still a single-center study, so I would not necessarily call it a validation, but it was certainly an expansion study to expand the number of patients from 62 to 202. And, again, the association still generally held up.
Transcript Edited for Clarity