Development and validation of circulating tumour cell enumeration (Epic Sciences) as a prognostic biomarker in men with metastatic castration-resistant prostate cancer.

Purpose: To evaluate the prognostic significance of circulating tumour cell (CTC) number determined on the Epic Sciences platform in men with metastatic castration-resistant prostate cancer (mCRPC) treated with an androgen receptor signalling inhibitor (ARSI).
Patients and Methods: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a first-, second- or third-line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N = 171) or as a first- or second-line therapy as part of the multicenter PROPHECY trial (NCT02269982) (Validation cohort, N = 107). The measured CTC number was then associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. CTC enumeration was also performed on a concurrently obtained blood sample using the CellSearch® Circulating Tumor Cell Kit.
Results: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (<3 CTCs/mL versus ≥ 3 CTCs/mL; hazard ratio [HR] = 1.8 [95% confidence interval {CI} 1.3-3.0]) and a continuous variable when adjusting for line of therapy, presence of visceral metastases, prostate-specific antigen, lactate dehydrogenase and alkaline phosphatase. The findings were validated in an independent datas et from PROPHECY (HR [95% CI] = 1.8 [1.1-3.0] for OS and 1.7 [1.1-2.9] for PFS). A strong correlation was also observed between CTC counts determined in matched samples on the CellSearch® and Epic platforms (r = 0.84).
Conclusion: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.
Competing Interests: Conflict of interest statement Howard I. Scher, leadership: Asterias Biotherapeutics; stock options and other ownership interests: Asterias Biotherapeutics; honoraria: Research to Practice, consulting or advisory role: Ambry Genetics/Konica Minolta; Amgen; Bayer; ESSA; Janssen; Janssen Research & Development; Menarini Silicon Biosystems; Pfizer; WIRB-Copernicus Group, research Funding: Epic Sciences (Inst); Illumina (Inst); Janssen (Inst); Menarini Silicon Biosystems (Inst); Thermo Fisher Scientific Biomarkers (Inst); Patents, Royalties, Other Intellectual Property - BioNTech -Intellectual Property Rights; Elucida Oncology: Intellectual Property Rights; MabVAX - Intellectual Property Rights; Y-mAbs Therapeutics, Inc - Intellectual Property Rights; travel, accommodations, expenses: Amgen; Asterias Biotherapeutics; Bayer; ESSA; Konica Minolta; Menarini Silicon Biosystems; Phosplatin Therapeutics; Prostate Cancer Foundation; Sanofi; WIRB-Copernicus Group. Andrew J. Armstrong, honoraria: Astellas Scientific and Medical Affairs Inc. consulting or advisory role: Astellas Scientific and Medical Affairs Inc; AstraZeneca; Bayer; Bristol-Myers Squibb; Clovis Oncology; Clovis Oncology; Dendreon; Merck; Pfizer; Speakers' Bureau: Bayer; research Funding: Astellas Pharma (Inst); AstraZeneca (Inst); Bayer (Inst); BeiGene (Inst); Bristol-Myers Squibb (Inst); Bristol-Myers Squibb (Inst); Constellation Pharmaceuticals (Inst); Dendreon (Inst); Gilead Sciences (Inst); Janssen Oncology (Inst); Merck (Inst); Novartis (Inst); Pfizer (Inst); Roche/Genentech (Inst); Patents, Royalties, Other Intellectual Property: Circulating tumour cell novel capture technology (Inst); travel, accommodations, expenses: Astellas Scientific and Medical Affairs Inc. Joseph D. Schonhoft employment: Epic Sciences; stock and other ownership interests - Epic Sciences. Audrey Gill: employment: Epic Sciences; stock and other ownership interests: Epic Sciences; consulting or advisory role - Epic Sciences; Epic Sciences (I); travel, accommodations, expenses - Epic Sciences. Jimmy Zhao has no conflicts of interest to disclose. Ethan Barnett stock and other ownership interests - Biondvax; Gilead Sciences. Emily Carbone has no conflicts of interest to disclose. James Lu employment - Epic Sciences; stock and other ownership interests - Epic Sciences. Emmanuel S. Antonarakis honoraria - Astellas Pharma; AstraZeneca; Clovis Oncology; Dendreon; ESSA; Janssen Biotech; Medivation; Merck; Sanofi; consulting or advisory role - AstraZeneca; Bayer; Clovis Oncology; Dendreon; ESSA; Janssen Biotech; Lilly; Merck; Sanofi; research Funding - Aragon Pharmaceuticals (Inst); Astellas Pharma (Inst); AstraZeneca (Inst); Clovis Oncology (Inst); Constellation Pharmaceuticals (Inst); Dendreon (Inst); Exelixis (Inst); Genentech (Inst); Janssen Biotech (Inst); Johnson & Johnson (Inst); Merck (Inst); Millennium (Inst); Novartis (Inst); Sanofi (Inst); Tokai Pharmaceuticals (Inst); patents, royalties, other intellectual property - Co-inventor of a biomarker technology that has been licenced to Qiagen; travel, accommodations, expenses - Dendreon; Medivation; Sanofi. Jun Luo consulting or advisory role - Janssen Oncology; Sun Pharma; Tolero Pharmaceuticals; research Funding- Astellas Pharma (Inst); Calibr (Inst); cardiff Oncology (Inst); Constellation Pharmaceuticals (Inst); Gilead Sciences (Inst); Mirati Therapeutics (Inst); Orion Pharma GmbH (Inst); Sanofi (Inst); patents, royalties, other intellectual property - Jun Luo is a co-inventor of a technology assigned to Johns Hopkins University who licenced to Tokai Pharmaceuticals (Inst); Jun Luo is a co-inventor of a technology licenced to A&G Pharmaceuticals (Inst); Jun Luo is a co-inventor of a technology licenced to Qiagen (Inst); Scott T. Tagawa consulting or advisory role: Abbvie; Amgen; Astellas Pharma; Bayer; Blue Earth Diagnostics; Clovis Oncology; Dendreon; Endocyte; Genentech; Genomic Health; Immunomedics; Janssen; Karyopharm Therapeutics; Medivation; Novartis; Pfizer; POINT Biopharma; QED Therapeutics; Sanofi; Tolmar; research Funding - Abbvie (Inst); Amgen (Inst); Astellas Pharma (Inst); AstraZeneca (Inst); AVEO (Inst); Bayer (Inst); Boehringer Ingelheim (Inst); Bristol-Myers Squibb (Inst); Clovis Oncology (Inst); Dendreon (Inst); Endocyte (Inst); Exelixis (Inst); Genentech (Inst); Immunomedics (Inst); Inovio Pharmaceuticals (Inst); Janssen (Inst); Karyopharm Therapeutics (Inst); Lilly (Inst); Medivation (Inst); Merck (Inst); Millennium (Inst); Newlink Genetics (Inst); Novartis (Inst); Progenics (Inst); Rexahn Pharmaceuticals (Inst); Sanofi (Inst); Stem CentRx (Inst); travel, accommodations, expenses - Amgen; Immunomedics; Sanofi. (OPTIONAL) Uncompensated Relationships - ATLAB Pharma; Phosplatin Therapeutics; Telix Pharmaceuticals. Qian Yang has no conflicts of interest to disclose. Daniel J. George leadership - Capio BioSciences; honoraria - Acceleron Pharma; American Association for Cancer Research; Axess Oncology; Bayer; EMD Serono; Exelixis; Janssen Oncology; Millennium Medical Publishing; OncLive; Pfizer; Sanofi; UroToday; consulting or advisory role - Astellas Pharma; AstraZeneca; Bayer; Bristol-Myers Squibb; Constellation Pharmaceuticals; Exelixis; Genentech; Innocrin Pharma; Janssen; Merck Sharp & Dohme; Michael J. Hennessy Associates; Myovant Sciences; Pfizer; Sanofi; Vizuri; speakers' bureau - Bayer; Exelixis; Sanofi; research Funding- Acerta Pharma (Inst); Astellas Pharma (Inst); Bayer (Inst); Bristol-Myers Squibb (Inst); Calithera Biosciences (Inst); Dendreon (Inst); Exelixis (Inst); Innocrin Pharma (Inst); Janssen Oncology (Inst); Novartis (Inst); Pfizer (Inst); Sanofi/Aventis (Inst); travel, accommodations, expenses - Bayer; Exelixis; Janssen Oncology; Merck; Pfizer; Sanofi; UroToday. Russell Zelig Szmulewitz honoraria - Astellas Pharma; consulting or advisory role - Abbvie; Amgen; Astellas Pharma; AstraZeneca; Exelixis; Janssen Oncology; Merck; Pfizer; Sanofi; research Funding - Abbvie; Astellas Pharma; Incyte; Janssen Oncology; Macrogenics; patents, royalties, other intellectual property - Patent licenced by University of Chicago of which I am co-inventor to Corcept Therapeutics for combination AR/GR inhibition in prostate cancer; travel, accommodations, expenses - Corcept Therapeutics. Daniel Costin Danila honoraria - Angle; Astellas Pharma; AxImmune; Bayer; Clovis Oncology; Janssen Oncology; Pfizer; Pfizer; ScreenCell; consulting or advisory role - Angle; Astellas Pharma; AxImmune; Bayer; Clovis Oncology; Janssen Scientific Affairs; Pfizer; Pfizer; Sanador; research Funding - Genentech; Janssen Research & Development (Inst); Prostate Cancer Foundation; patents, royalties, other intellectual property - GENE EXPRESSION PROFILE ASSOCIATED WITH PROSTATE CANCER; travel, accommodations, expenses - American Austrian Open Medical Institute; Astellas Pharma; Cambridge Healthtech Institute; Genzyme; Janssen Biotech; Janssen Scientific Affairs; Pfizer; Prostate Cancer Foundation; ScreenCell; Stop Cancer. Rick Wenstrup employment - Epic Sciences; leadership - Epic Sciences; stock and other ownership interests - Epic Sciences; Epic Sciences; consulting or advisory role - Blueprint Genetics; Resolys Bio; patents, royalties, other Intellectual Property - patent royalties, AssurexHealth; travel, accommodations, expenses - Epic Systems. Mithat Gonen has np conflicts of interest to disclose. Susan Halabi employment - ASCO; consulting or advisory role - Eisai; Ferring.
(Copyright © 2021. Published by Elsevier Ltd.)