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2018 ASCO Annual Meeting!

Session: Genitourinary (Prostate) Cancer

Type: Oral Abstract Session

Time: Monday June 4, 3:00 PM to 6:00 PM

Location: Hall D1

The PROPHECY trial: Multicenter prospective trial of circulating tumor cell (CTC) AR-V7 detection in men with mCRPC receiving abiraterone (A) or enzalutamide (E).


Genitourinary (Prostate) Cancer

2018 ASCO Annual Meeting

Abstract No:

J Clin Oncol 36, 2018 (suppl; abstr 5004)

Author(s): Andrew J. Armstrong, Susan Halabi, Jun Luo, David M. Nanus, Paraskevi Giannakakou, Russell Zelig Szmulewitz, Daniel Costin Danila, Patrick Healy, Monika Anand, Colin Rothwell, John Silberstein, Giuseppe Galletti, Jason Somarelli, Santosh Gupta, Simon Gregory, Howard I. Scher, Ryan Dittamore, Scott T. Tagawa, Emmanuel S. Antonarakis, Daniel J. George; Duke Cancer Institute, Duke University, Durham, NC; Duke University Medical Center, Durham, NC; James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD; Sandra and Edward Meyer Cancer Center, New York, NY; Weill Cornell Medicine/Meyer Cancer Center, New York, NY; The University of Chicago, Chicago, IL; Memorial Sloan Kettering Cancer Center, New York, NY; Duke University, Durham, NC; Stanford University, Stanford, CA; Duke University Center for Human Genetics, Durham, NC; Epic Sciences, Inc., San Diego, CA; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD

Abstract Disclosures


Background: It is unclear if CTC AR-V7 detection is a valid predictive biomarker of clinical efficacy in men with mCRPC receiving A/E or just an indicator of aggressive disease and high tumor burden. Methods: We conducted a multicenter prospective study of circulating biomarkers in men with high-risk mCRPC (PROPHECY, NCT02269982) starting A/E. The primary endpoint was association of baseline AR-V7 with radiographic/clinical progression free survival (PFS), using the Johns Hopkins modified-AdnaTest CTC AR-V7 mRNA assay and the Epic Sciences CTC nuclear AR-V7 protein assay. Overall survival (OS) and PSA decline were key secondary endpoints. Results: We enrolled 118 men with mCRPC starting A/E; 52% had ≥5 Cellsearch CTCs, 36% had prior A/E. On study therapy was A (n = 56), E (n = 59) or both A/E (n = 3). AR-V7 detection by the JHU AR-V7 assay and the Epic AR-V7 assay were independently associated with worse PFS and OS after adjusting for CTC count and established clinical factors (see below table). Concordance between the two AR-V7 assays was 82%. Epic AR-V7 (+) men had more CTC phenotypic heterogeneity: 63% had Shannon Index > 1.5 vs 14% of AR-V7 (-) men; most CTCs in Epic AR-V7 (+) men were AR-V7 (-). We found genetic alterations of aggressive mCRPC in AR-V7 (+) and AR-V7 (-) men including gain of AR, MYCN, and MYC and loss of PTEN, TP53, and DNA repair enzymes in CTCs and ctDNA. Conclusions: We validate AR-V7 detection as an independent CTC-adjusted negative predictive biomarker of short PFS and OS with A/E treatment in men with mCRPC, identify CTC heterogeneity of AR-V7 expression, and highlight the importance of non-AR-V7 drivers of aggressive disease. Clinical trial information: NCT02269982

OutcomeAR-V7 (JHU n = 116)
(+) n = 28 (24%) / (-) n = 88 (66%)
AR-V7 (Epic n = 105)
(+) n = 11 (10%) / (-) n = 94 (90%)
Median PFS (mo)3.1 / 7.33.1 / 6.0
HR* (95% CI)2.4 (1.6-3.8)2.4 (1.3-4.6)
HR˚(95% CI)2.4 (1.4-3.9)2.2 (1.0-4.9)
Median OS (mo)11.5 / 25.58.4 / 25.5
HR*(95% CI)3.9 (2.1- 7.3)4.5 (2.1-9.8)
HR˚ (95% CI4.6 (2.3-9.2)3.6 (1.5-8.6)
≥ 50% confirmed PSA decline11% / 28%0% / 26%
Odds Ratio (95% CI)0.31 (0.09-1.12)Not estimable

*univariate, ˚adjusted for Cellsearch CTC enumeration, PSA, Alk Phos, Hgb

Other Abstracts in this Sub-Category:


1. Six-month patient-reported outcome (PRO) results from AQUARiUS, a prospective, observational, multicenter phase 4 study in patients (Pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone acetate + prednisone (AAP) or enzalutamide (ENZ).

Meeting: 2018 ASCO Annual Meeting Abstract No: 5058 First Author: Antoine Thiery Vuillemin
Category: Genitourinary (Prostate) Cancer - Biomarkers/Epidemiology/Outcomes


2. Expression of immune checkpoints (ICs) on circulating tumor cells (CTCs) in men with metastatic prostate cancer (mPC).

Meeting: 2018 ASCO Annual Meeting Abstract No: 5059 First Author: Tian Zhang
Category: Genitourinary (Prostate) Cancer - Biomarkers/Epidemiology/Outcomes


3. The association of BRCA1 and BRCA2 mutations on prostate cancer risk, frequency, and mortality: Systematic review and meta-analysis.

Meeting: 2018 ASCO Annual Meeting Abstract No: 5060 First Author: Mok Oh
Category: Genitourinary (Prostate) Cancer - Biomarkers/Epidemiology/Outcomes