Christof Bernemann1, Thomas J Schnoeller2, Manuel Luedeke2, Konrad Steinestel3, Martin Boegemann1, Andres J Schrader1, Julie Steinestel4. 1. Clinic of Urology, University Hospital Muenster, Muenster, Germany. 2. Clinic of Urology, University Hospital Ulm, Ulm, Germany. 3. Gerhard-Domagk-Institute of Pathology, University Hospital Muenster, Muenster, Germany. 4. Clinic of Urology, University Hospital Muenster, Muenster, Germany. Electronic address: julie.steinestel@ukmuenster.de.
Abstract
The androgen receptor splice variant AR-V7 has recently been discussed as a predictive biomarker for nonresponse to next-generation androgen deprivation therapy (ADT) in patients with castration-resistant prostate cancer. However, we recently identified one patient showing a response from abiraterone despite expression of AR-V7 in his circulating tumour cells (CTC). Therefore, we precisely assessed the response in a cohort of 21 AR-V7 positive castration-resistant prostate cancer patients who had received therapy with abiraterone or enzalutamide. We detected a subgroup of six AR-V7 positive patients showing benefit from either abiraterone or enzalutamide. Their progression free survival was 26 d (censored) to 188 d. Four patients displayed a prostate-specific antigen decrease of >50%. When analysing prior therapies, we noticed that only one of the six patients had received next-generation ADT prior to CTC collection. As a result, we conclude that AR-V7 status in CTC cannot entirely predict nonresponse to next generation ADT and AR-V7-positive patients should not be systematically denied abiraterone or enzalutamide treatment, especially as effective alternative treatment options are still limited. PATIENT SUMMARY: A subgroup of patients can benefit from abiraterone and/or enzalutamide despite detection of AR-V7 splice variants in their circulating tumour cells.
The androgen receptor splice variant AR-V7 has recently been discussed as a predictive biomarker for nonresponse to next-generation androgen deprivation therapy (ADT) in patients with castration-resistant prostate cancer. However, we recently identified one patient showing a response from abiraterone despite expression of AR-V7 in his circulating tumour cells (CTC). Therefore, we precisely assessed the response in a cohort of 21 AR-V7 positive castration-resistant prostate cancerpatients who had received therapy with abiraterone or enzalutamide. We detected a subgroup of six AR-V7 positive patients showing benefit from either abiraterone or enzalutamide. Their progression free survival was 26 d (censored) to 188 d. Four patients displayed a prostate-specific antigen decrease of >50%. When analysing prior therapies, we noticed that only one of the six patients had received next-generation ADT prior to CTC collection. As a result, we conclude that AR-V7 status in CTC cannot entirely predict nonresponse to next generation ADT and AR-V7-positive patients should not be systematically denied abiraterone or enzalutamide treatment, especially as effective alternative treatment options are still limited. PATIENT SUMMARY: A subgroup of patients can benefit from abiraterone and/or enzalutamide despite detection of AR-V7 splice variants in their circulating tumour cells.
Authors: Howard I Scher; Ryon P Graf; Nicole A Schreiber; Anuradha Jayaram; Eric Winquist; Brigit McLaughlin; David Lu; Martin Fleisher; Sarah Orr; Lori Lowes; Amanda Anderson; Yipeng Wang; Ryan Dittamore; Alison L Allan; Gerhardt Attard; Glenn Heller Journal: JAMA Oncol Date: 2018-09-01 Impact factor: 31.777
Authors: Emmanuel S Antonarakis; Jun Luo; Andrew J Armstrong; Landon C Brown; Changxue Lu Journal: Prostate Cancer Prostatic Dis Date: 2020-02-24 Impact factor: 5.554