Meeting
2020 Genitourinary Cancers Symposium
Association of circulating tumor cell chromosomal instability with worse outcomes in men with mCRPC treated with abiraterone or enzalutamide.
Authors
Landon Carter Brown
Duke Cancer Institute, Durham, NC
Landon Carter Brown , Susan Halabi , Joseph Schonhoft , Jun Luo , David M. Nanus , Paraskevi Giannakakou , Daniel Costin Danila , Patrick Healy , Monika Anand , Jason Somarelli , Howard I. Scher , Rick Wenstrup , William R. Berry , Scott T. Tagawa , Emmanuel S. Antonarakis , Daniel J. George , Andrew J. Armstrong , Russell Zelig Szmulewitz
Organizations
Duke Cancer Institute, Durham, NC, Duke University Medical Center, Durham, NC, Epic Sciences, Inc., San Diego, CA, 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, Memorial Sloan Kettering Cancer Center, New York, NY, Duke University, Durham, NC, Epic Sciences, San Diego, CA, Duke University School of Medicine, Cary, NC, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, Duke University School of Medicine, Durham, NC, Department of Medicine, The University of Chicago, Chicago, IL
Research Funding
Other Foundation
Prostate Cancer Foundation, Other Foundation, U.S. National Institutes of Health
Background: While AR-V7 is a known driver of hormonal resistance, most men with mCRPC lack AR-V7 detection and commonly experience cross-resistance to abiraterone and enzalutamide (abi/enza). Loss of AR dependence through neuroendocrine (NE) differentiation or chromosomal instability (CIN) may explain AR therapy cross-resistance in additional men. Methods: PROPHECY was a multicenter prospective study of men with poor risk mCRPC starting abi/enza. We assessed Epic CTC AR-V7, CIN and NE phenotypes before abi/enza and at progression. Radiographic/clinical progression free survival (PFS) and overall survival (OS) were associated with CIN (>3 CTCs) and NE (>3 CTCs) CTC phenotypes using the proportional hazards model adjusting for Cellsearch CTC, AR-V7, and clinical risk score. Results: 118 men with mCRPC starting on abi/enza were enrolled; 106 had evaluable CTCs for AR-V7, CIN, and NE on the Epic platform. Of these, 22.6% and 9.4% of men exhibited high CTC CIN and NE scores, respectively. High pre-treatment CIN and NE phenotypic scores were observed in 63 and 27% of AR-V7 (+) and in 17 and 7% of AR-V7 (-) men. CTC CIN phenotype but not NE phenotype was associated with a lower confirmed PSA response rate and OS (TABLE) with abi/enza, adjusting for CTC number, AR-V7 and risk score. Conclusions: A high chromosomal instability CTC phenotype is associated with worse outcomes in men with mCRPC treated with abi/enza and warrants further study as a prognostic or predictive biomarker. Clinical trial information: NCT02269982
| Chromosomal Instability Phenotype n=106 | Neuroendocrine Phenotype n= 106 | |||
|---|---|---|---|---|
| Positive | Negative | Positive | Negative | |
| All Men | 24 (22.6%) | 82 (77.4%) | 10 (9.4%) | 96 (90.6%) |
| Epic Nuclear AR-V7 (+) | 7 (63.6%) | 4 (36.3%) | 3 (27.3%) | 8 (72.3%) |
| Median PFS (mo; 95% CI) | 4.1 (2.4-5.7) | 6.6 (4.1-8.5) | 3.3 (1.1-5.7) | 5.9 (4.1-7.8) |
| HR* (95% CI) | 2.1 (1.3-3.5) | 2.1 (1.1-4.1) | ||
| HR**(95% CI) | 1.1 (0.6-2.3) | 1.0 (0.4-2.4) | ||
| Median OS (mo; 95% CI) | 11.5 (7.2-14.9) | 25.0 (18.5-28.0) | 8.3 (1.3-25.0) | 20.0 (16.9-25.8) |
| HR*(95% CI) | 3.4 (2.0-5.6) | 2.4 (1.2-4.7) | ||
| HR** (95% CI) | 2.1 (1.1-4.1) | 0.8 (0.4-1.8) | ||
| ≥ 50% confirmed PSA decline (95% CI) | 16% (3-40) | 30% (19-42) | 25% (3-65) | 27% (17-38) |
*univariate, **adjusted for Cellsearch CTCs (>5), AR-V7, risk score
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Abstract Details
Session Type
Poster Session
Session Title
Poster Session A: Prostate Cancer
Track
Prostate Cancer - Advanced,Prostate Cancer - Localized
Sub Track
Tumor Biology, Biomarkers, and Pathology
Clinical Trial Registration Number
NCT02269982
Citation
J Clin Oncol 38, 2020 (suppl 6; abstr 183)
Abstract #
183
Poster Bd #
H19
Abstract Disclosures
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