Abstract 3363
Background
AR-V7 is a truncated form of the AR lacking the ligand binding domain that activates AR signaling in the absence of androgens. The presence of AR-V7 mRNA in CTCs predicts a poor outcome on the ARSi, abiraterone and enzalutamide. Localization of AR-V7 in the nucleus of CTCs also predicts poor ARSi outcomes, and a treatment-specific interaction that predicted a reduced risk of death if Taxanes vs. ARSi (HR = 0.242, p = 0.0350) are prescribed. Overall, the incidence of nuclear AR-V7 protein was lower than that of AR-V7 mRNA, but more predictive of ARSi outcomes. In a post-hoc analysis of outcomes of samples evaluated with AR-V7 CTC protein we asked if the presence of cytoplasmic AR-V7 protein could explain the difference in prognostic ability of the two tests, and separately, explored the association between non-nuclear AR-V7 and benefit from taxanes over ARSi.
Methods
191 blood samples (n = 128 pre-ARSi, n = 63 pre-Taxane) from 161 patients were processed utilizing the Epic Sciences CTC nuclear AR-V7 protein test. Patients were followed up to 29.5 months (range 1.3 to 29.5). Samples were rescored by readers, blinded to outcome to determine the frequency of and outcome with cytoplasmic AR-V7.
Results
Inclusion of non-nuclear localized AR-V7 protein as positive scoring criteria increased the incidence of detection in all lines of therapy, an equivalent increase in false positives (PSA responders), and loss of the significance of the treatment-specific survival interaction in multivariate model.
| AR-V7 Localization | Detection Rate by Line of Therapy (1st, 2nd, 3rd +) | HR of OS on ARSi | Therapy Interaction (Taxanes vs. ARSi) |
|---|---|---|---|
| Nuclear (alone) | 3%, 18%, 31% | 11.5, p ConclusionsIncluding cytoplasmic AR-V7 in the “positive” test definition reduces the prognostic power of the assay and negates the treatment predictive value of AR-V7. Not all AR-V7 signal is equivalent. It remains to be seen if non-nuclear localized AR-V7 protein samples would test positive via mRNA methods. Clinical trial identificationLegal entity responsible for the studyMemorial Sloan Kettering Cancer Center FundingEpic Sciences DisclosureH. Scher: Consulting: Astellas, AstraZeneca, BIND Therapeutics, Blue Earth, Bristol-Myers Squibb, Chugai, Endocyte, Ferring, Genentech, Janssen, Med IQ, Medivation, OncologySTAT, Palmetto GBA, Pfizer, Sanofi, Takeda, Ventana, WIRB-Copernicus Group. R. Graf, D. Lu, J. Louw, R. Dittamore: Epic Sciences Employee. All other authors have declared no conflicts of interest. Resources from the same session3202 - PTEN loss as a predictive biomarker for the Akt inhibitor ipatasertib combined with abiraterone acetate in patients with metastatic castration-resistant prostate cancer (mCRPC)Presenter: Johann de Bono Session: Genitourinary tumours, prostate Resources: Abstract Slides Invited discussant abstracts 717O and 718OPresenter: Felix Feng Session: Genitourinary tumours, prostate Resources: Slides Invited discussant abstracts LBA29 and 719OPresenter: Winald Gerritsen Session: Genitourinary tumours, prostate Resources: Slides 2636 - Metastasis free survival (MFS) is a surrogate for overall survival (OS) in localized prostate cancer (CaP)Presenter: Wanling Xie Session: Genitourinary tumours, prostate Resources: Abstract 1863 - A phase 2 study of the aurora kinase A inhibitor alisertib for patients with neuroendocrine prostate cancer (NEPC)Presenter: Himisha Beltran Session: Genitourinary tumours, prostate Resources: Abstract Slides 1905 - First evidence of significant clinical activity of PD-1 inhibitors in metastatic, castration resistant prostate cancer (mCRPC)Presenter: Julie Graff Session: Genitourinary tumours, prostate Resources: Abstract 2243 - Long term efficacy and QOL data of chemohormonal therapy (C-HT) in low and high volume hormone naïve metastatic prostate cancer (PrCa): E3805 CHAARTED trialPresenter: Christopher Sweeney Session: Genitourinary tumours, prostate Resources: Abstract 3045 - FIRSTANA: Health-related quality of life (HRQL) and post-hoc analyses for the phase III study assessing cabazitaxel (C) vs docetaxel (D) in chemotherapy-naïve patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)Presenter: Stephane Oudard Session: Genitourinary tumours, prostate Resources: Abstract 2907 - PROSELICA: Health-related quality of life (HRQL) and post-hoc analyses for the phase 3 study assessing cabazitaxel 20 (C20) vs 25 (C25) mg/m2 post-docetaxel (D) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)Presenter: Johann de Bono Session: Genitourinary tumours, prostate Resources: Abstract 2161 - Modelling relapse in patients with high-risk localised prostate cancer treated randomly in the GETUG 12 phase III trial reveals two populations of relapsing patientsPresenter: Cécile Vicier Session: Genitourinary tumours, prostate Resources: Abstract This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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