Transcriptional profiling of primary prostate tumor in metastatic hormone-sensitive prostate cancer and association with clinical outcomes: correlative analysis of the E3805 CHAARTED trial

A. A. Hamid; H. C. Huang; V. Wang; Y. H. Chen; F. Feng; R. Den; G. Attard; E. M. Van Allen; P. T. Tran; D. E. Spratt; R. Dittamore; E. Davicioni; G. Liu; R. DiPaola; M. A. Carducci; C. J. Sweeney

doi:10.1016/j.annonc.2021.06.003

Transcriptional profiling of primary prostate tumor in metastatic hormone-sensitive prostate cancer and association with clinical outcomes: correlative analysis of the E3805 CHAARTED trial

A. A. Hamid, H. C. Huang, V. Wang, Y. H. Chen, F. Feng, R. Den, G. Attard, E. M. Van Allen, P. T. Tran, D. E. Spratt, R. Dittamore, E. Davicioni, G. Liu, R. DiPaola, M. A. Carducci, C. J. Sweeney

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

Abstract

Background: The phase III CHAARTED trial established upfront androgen-deprivation therapy (ADT) plus docetaxel (D) as a standard for metastatic hormone-sensitive prostate cancer (mHSPC) based on meaningful improvement in overall survival (OS). Biological prognostic markers of outcomes and predictors of chemotherapy benefit are undefined. Patients and methods: Whole transcriptomic profiling was performed on primary PC tissue obtained from patients enrolled in CHAARTED prior to systemic therapy. We adopted an a priori analytical plan to test defined RNA signatures and their associations with HSPC clinical phenotypes and outcomes. Multivariable analyses (MVAs) were adjusted for age, Eastern Cooperative Oncology Group status, de novo metastasis presentation, volume of disease, and treatment arm. The primary endpoint was OS; the secondary endpoint was time to castration-resistant PC. Results: The analytic cohort of 160 patients demonstrated marked differences in transcriptional profile compared with localized PC, with a predominance of luminal B (50%) and basal (48%) subtypes, lower androgen receptor activity (AR-A), and high Decipher risk disease. Luminal B subtype was associated with poorer prognosis on ADT alone but benefited significantly from ADT + D [OS: hazard ratio (HR) 0.45; P = 0.007], in contrast to basal subtype which showed no OS benefit (HR 0.85; P = 0.58), even in those with high-volume disease. Higher Decipher risk and lower AR-A were significantly associated with poorer OS in MVA. In addition, higher Decipher risk showed greater improvements in OS with ADT + D (HR 0.41; P = 0.015). Conclusion: This study demonstrates the utility of transcriptomic subtyping to guide prognostication in mHSPC and potential selection of patients for chemohormonal therapy, and provides proof of concept for the possibility of biomarker-guided selection of established combination therapies in mHSPC.

Original language	English
Pages (from-to)	1157-1166
Number of pages	10
Journal	Annals of Oncology
Volume	32
Issue number	9
DOIs	https://doi.org/10.1016/j.annonc.2021.06.003
State	Published - Sep 2021

Bibliographical note

Funding Information:
This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O’Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: U10CA180820 , U10CA180794 , UG1CA233160 , UG1CA233180 , UG1CA233196 , UG1CA233277 , UG1CA233341 . The study was also supported by Sanofi . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mention of trade names, commercial products, or organizations does not imply endorsement by the US government.

Funding Information:
Decipher Biosciences: In-kind support for Decipher microarray profiling and data generation. AAH: supported by Prostate Cancer Foundation Young Investigator Award [grant number 18YOUN07 ]; National Health and Medical Research Council Australia (no grant number), Department of Defense Early Investigator Research Award [grant number W81XWH2010055 ]. CJS: Supported by National Institutes of Health Research Project Grant Program [grant number NIH R01 CA238020-01A1 ].

Funding Information:
This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O'Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: U10CA180820, U10CA180794, UG1CA233160, UG1CA233180, UG1CA233196, UG1CA233277, UG1CA233341. The study was also supported by Sanofi. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mention of trade names, commercial products, or organizations does not imply endorsement by the US government. Decipher Biosciences: In-kind support for Decipher microarray profiling and data generation. AAH: supported by Prostate Cancer Foundation Young Investigator Award [grant number 18YOUN07]; National Health and Medical Research Council Australia (no grant number), Department of Defense Early Investigator Research Award [grant number W81XWH2010055]. CJS: Supported by National Institutes of Health Research Project Grant Program [grant number NIH R01 CA238020-01A1]. A.A.H reports consulting fees from Merck Sharp & Dohme. H-C.H. R.D. and E.D. are employees of Decipher Biosciences. F.F. reports receiving fees for serving as a consultant from Janssen during the conduct of the study, Celgene, Blue Earth Diagnostics, Astellas, Myovant, Roivant, Genentech, and Bayer; being a co-founder having stock options in PFS Genomics; and having stock options and serving on the scientific advisory board of SerImmune Stock outside the submitted work. G.A. reports personal fees, research support and travel support from Janssen during the conduct of the study; personal fees and/or travel support from Astellas, Pfizer, Millennium Pharmaceuticals, Ipsen, Ventana, Veridex, Novartis, Abbott Laboratories, ESSA Pharmaceuticals, Bayer Healthcare Pharmaceuticals, Takeda and Sanofi-Aventis and research funding from AstraZeneca, Innocrin Pharma and Arno Therapeutics outside the submitted work; in addition, G.A.?s former employer, The Institute of Cancer Research (ICR), receives royalty income from abiraterone acetate and GA receives a share of this income through ICR's Rewards to Discoverers scheme. E.M.V.A reports advisory/consulting role: Tango Therapeutics, Genome Medical, Invitae, Enara Bio, Janssen, Manifold Bio, Monte Rosa; research support: Novartis, BMS; equity: Tango Therapeutics, Genome Medical, Syapse, Enara Bio, Manifold Bio, Microsoft, Monte Rosa; travel reimbursement: Roche/Genentech; patents: Institutional patents filed on chromatin mutations and immunotherapy response, and methods for clinical interpretation. P.T.T. reported receiving grants from RefleXion Medical, the Prostate Cancer Foundation, and Movember Foundation; personal fees from Noxopharm, Janssen-Taris Biomedical, Myovant, AstraZeneca, and RefleXion; grants from Astellas and Bayer Healthcare; and owning patent No. 9114158 (with royalties from Natsar Pharmaceuticals) outside the submitted work. D.E.S reports personal fees: Janssen, AstraZeneca, Bayer, Boston Scientific, and Blue Earth; funding: Janssen. G.L. is a co-founder and chief medical officer of AIQ Solutions (Madison, WI). M.A.A. reports past consultation for Pfizer, Astellas, and Exelixis, and current research funding from Arcus, Pfizer, and Merck. C.J.S. report consulting or advisory role: Sanofi, Janssen, Astellas Pharma, Bayer, Genentech, Pfizer, Lilly; research funding: Janssen Biotech (Inst), Astellas Pharma (Inst), Sanofi (Inst), Bayer (Inst), Sotio (Inst), Dendreon (Inst); patents, royalties, other intellectual property: Pathenolide (Indiana University): dimethylaminoparthenolide (Leuchemix); Exelixis: Abiraterone plus cabozantinib combination; stock or other ownership: Leuchemix.

Publisher Copyright:
© 2021 The Authors

Keywords

Decipher
biomarker
docetaxel
gene expression profiling
metastatic prostate cancer

ASJC Scopus subject areas

Hematology
Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.annonc.2021.06.003

Cite this

Hamid, A. A., Huang, H. C., Wang, V., Chen, Y. H., Feng, F., Den, R., Attard, G., Van Allen, E. M., Tran, P. T., Spratt, D. E., Dittamore, R., Davicioni, E., Liu, G., DiPaola, R., Carducci, M. A., & Sweeney, C. J. (2021). Transcriptional profiling of primary prostate tumor in metastatic hormone-sensitive prostate cancer and association with clinical outcomes: correlative analysis of the E3805 CHAARTED trial. Annals of Oncology, 32(9), 1157-1166. https://doi.org/10.1016/j.annonc.2021.06.003

@article{56c0780496a340a1b2a30b3684d6529a,

title = "Transcriptional profiling of primary prostate tumor in metastatic hormone-sensitive prostate cancer and association with clinical outcomes: correlative analysis of the E3805 CHAARTED trial",

abstract = "Background: The phase III CHAARTED trial established upfront androgen-deprivation therapy (ADT) plus docetaxel (D) as a standard for metastatic hormone-sensitive prostate cancer (mHSPC) based on meaningful improvement in overall survival (OS). Biological prognostic markers of outcomes and predictors of chemotherapy benefit are undefined. Patients and methods: Whole transcriptomic profiling was performed on primary PC tissue obtained from patients enrolled in CHAARTED prior to systemic therapy. We adopted an a priori analytical plan to test defined RNA signatures and their associations with HSPC clinical phenotypes and outcomes. Multivariable analyses (MVAs) were adjusted for age, Eastern Cooperative Oncology Group status, de novo metastasis presentation, volume of disease, and treatment arm. The primary endpoint was OS; the secondary endpoint was time to castration-resistant PC. Results: The analytic cohort of 160 patients demonstrated marked differences in transcriptional profile compared with localized PC, with a predominance of luminal B (50%) and basal (48%) subtypes, lower androgen receptor activity (AR-A), and high Decipher risk disease. Luminal B subtype was associated with poorer prognosis on ADT alone but benefited significantly from ADT + D [OS: hazard ratio (HR) 0.45; P = 0.007], in contrast to basal subtype which showed no OS benefit (HR 0.85; P = 0.58), even in those with high-volume disease. Higher Decipher risk and lower AR-A were significantly associated with poorer OS in MVA. In addition, higher Decipher risk showed greater improvements in OS with ADT + D (HR 0.41; P = 0.015). Conclusion: This study demonstrates the utility of transcriptomic subtyping to guide prognostication in mHSPC and potential selection of patients for chemohormonal therapy, and provides proof of concept for the possibility of biomarker-guided selection of established combination therapies in mHSPC.",

keywords = "Decipher, biomarker, docetaxel, gene expression profiling, metastatic prostate cancer",

author = "Hamid, {A. A.} and Huang, {H. C.} and V. Wang and Chen, {Y. H.} and F. Feng and R. Den and G. Attard and {Van Allen}, {E. M.} and Tran, {P. T.} and Spratt, {D. E.} and R. Dittamore and E. Davicioni and G. Liu and R. DiPaola and Carducci, {M. A.} and Sweeney, {C. J.}",

note = "Funding Information: This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O{\textquoteright}Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: U10CA180820 , U10CA180794 , UG1CA233160 , UG1CA233180 , UG1CA233196 , UG1CA233277 , UG1CA233341 . The study was also supported by Sanofi . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mention of trade names, commercial products, or organizations does not imply endorsement by the US government. Funding Information: Decipher Biosciences: In-kind support for Decipher microarray profiling and data generation. AAH: supported by Prostate Cancer Foundation Young Investigator Award [grant number 18YOUN07 ]; National Health and Medical Research Council Australia (no grant number), Department of Defense Early Investigator Research Award [grant number W81XWH2010055 ]. CJS: Supported by National Institutes of Health Research Project Grant Program [grant number NIH R01 CA238020-01A1 ]. Funding Information: This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O'Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: U10CA180820, U10CA180794, UG1CA233160, UG1CA233180, UG1CA233196, UG1CA233277, UG1CA233341. The study was also supported by Sanofi. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mention of trade names, commercial products, or organizations does not imply endorsement by the US government. Decipher Biosciences: In-kind support for Decipher microarray profiling and data generation. AAH: supported by Prostate Cancer Foundation Young Investigator Award [grant number 18YOUN07]; National Health and Medical Research Council Australia (no grant number), Department of Defense Early Investigator Research Award [grant number W81XWH2010055]. CJS: Supported by National Institutes of Health Research Project Grant Program [grant number NIH R01 CA238020-01A1]. A.A.H reports consulting fees from Merck Sharp & Dohme. H-C.H. R.D. and E.D. are employees of Decipher Biosciences. F.F. reports receiving fees for serving as a consultant from Janssen during the conduct of the study, Celgene, Blue Earth Diagnostics, Astellas, Myovant, Roivant, Genentech, and Bayer; being a co-founder having stock options in PFS Genomics; and having stock options and serving on the scientific advisory board of SerImmune Stock outside the submitted work. G.A. reports personal fees, research support and travel support from Janssen during the conduct of the study; personal fees and/or travel support from Astellas, Pfizer, Millennium Pharmaceuticals, Ipsen, Ventana, Veridex, Novartis, Abbott Laboratories, ESSA Pharmaceuticals, Bayer Healthcare Pharmaceuticals, Takeda and Sanofi-Aventis and research funding from AstraZeneca, Innocrin Pharma and Arno Therapeutics outside the submitted work; in addition, G.A.?s former employer, The Institute of Cancer Research (ICR), receives royalty income from abiraterone acetate and GA receives a share of this income through ICR's Rewards to Discoverers scheme. E.M.V.A reports advisory/consulting role: Tango Therapeutics, Genome Medical, Invitae, Enara Bio, Janssen, Manifold Bio, Monte Rosa; research support: Novartis, BMS; equity: Tango Therapeutics, Genome Medical, Syapse, Enara Bio, Manifold Bio, Microsoft, Monte Rosa; travel reimbursement: Roche/Genentech; patents: Institutional patents filed on chromatin mutations and immunotherapy response, and methods for clinical interpretation. P.T.T. reported receiving grants from RefleXion Medical, the Prostate Cancer Foundation, and Movember Foundation; personal fees from Noxopharm, Janssen-Taris Biomedical, Myovant, AstraZeneca, and RefleXion; grants from Astellas and Bayer Healthcare; and owning patent No. 9114158 (with royalties from Natsar Pharmaceuticals) outside the submitted work. D.E.S reports personal fees: Janssen, AstraZeneca, Bayer, Boston Scientific, and Blue Earth; funding: Janssen. G.L. is a co-founder and chief medical officer of AIQ Solutions (Madison, WI). M.A.A. reports past consultation for Pfizer, Astellas, and Exelixis, and current research funding from Arcus, Pfizer, and Merck. C.J.S. report consulting or advisory role: Sanofi, Janssen, Astellas Pharma, Bayer, Genentech, Pfizer, Lilly; research funding: Janssen Biotech (Inst), Astellas Pharma (Inst), Sanofi (Inst), Bayer (Inst), Sotio (Inst), Dendreon (Inst); patents, royalties, other intellectual property: Pathenolide (Indiana University): dimethylaminoparthenolide (Leuchemix); Exelixis: Abiraterone plus cabozantinib combination; stock or other ownership: Leuchemix. Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = sep,

doi = "10.1016/j.annonc.2021.06.003",

language = "English",

volume = "32",

pages = "1157--1166",

number = "9",

}

Hamid, AA, Huang, HC, Wang, V, Chen, YH, Feng, F, Den, R, Attard, G, Van Allen, EM, Tran, PT, Spratt, DE, Dittamore, R, Davicioni, E, Liu, G, DiPaola, R, Carducci, MA & Sweeney, CJ 2021, 'Transcriptional profiling of primary prostate tumor in metastatic hormone-sensitive prostate cancer and association with clinical outcomes: correlative analysis of the E3805 CHAARTED trial', Annals of Oncology, vol. 32, no. 9, pp. 1157-1166. https://doi.org/10.1016/j.annonc.2021.06.003

TY - JOUR

T1 - Transcriptional profiling of primary prostate tumor in metastatic hormone-sensitive prostate cancer and association with clinical outcomes

T2 - correlative analysis of the E3805 CHAARTED trial

AU - Hamid, A. A.

AU - Huang, H. C.

AU - Wang, V.

AU - Chen, Y. H.

AU - Feng, F.

AU - Den, R.

AU - Attard, G.

AU - Van Allen, E. M.

AU - Tran, P. T.

AU - Spratt, D. E.

AU - Dittamore, R.

AU - Davicioni, E.

AU - Liu, G.

AU - DiPaola, R.

AU - Carducci, M. A.

AU - Sweeney, C. J.

N1 - Funding Information: This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O’Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: U10CA180820 , U10CA180794 , UG1CA233160 , UG1CA233180 , UG1CA233196 , UG1CA233277 , UG1CA233341 . The study was also supported by Sanofi . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mention of trade names, commercial products, or organizations does not imply endorsement by the US government. Funding Information: Decipher Biosciences: In-kind support for Decipher microarray profiling and data generation. AAH: supported by Prostate Cancer Foundation Young Investigator Award [grant number 18YOUN07 ]; National Health and Medical Research Council Australia (no grant number), Department of Defense Early Investigator Research Award [grant number W81XWH2010055 ]. CJS: Supported by National Institutes of Health Research Project Grant Program [grant number NIH R01 CA238020-01A1 ]. Funding Information: This study was conducted by the ECOG-ACRIN Cancer Research Group (Peter J. O'Dwyer, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported by the National Cancer Institute of the National Institutes of Health under the following award numbers: U10CA180820, U10CA180794, UG1CA233160, UG1CA233180, UG1CA233196, UG1CA233277, UG1CA233341. The study was also supported by Sanofi. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Mention of trade names, commercial products, or organizations does not imply endorsement by the US government. Decipher Biosciences: In-kind support for Decipher microarray profiling and data generation. AAH: supported by Prostate Cancer Foundation Young Investigator Award [grant number 18YOUN07]; National Health and Medical Research Council Australia (no grant number), Department of Defense Early Investigator Research Award [grant number W81XWH2010055]. CJS: Supported by National Institutes of Health Research Project Grant Program [grant number NIH R01 CA238020-01A1]. A.A.H reports consulting fees from Merck Sharp & Dohme. H-C.H. R.D. and E.D. are employees of Decipher Biosciences. F.F. reports receiving fees for serving as a consultant from Janssen during the conduct of the study, Celgene, Blue Earth Diagnostics, Astellas, Myovant, Roivant, Genentech, and Bayer; being a co-founder having stock options in PFS Genomics; and having stock options and serving on the scientific advisory board of SerImmune Stock outside the submitted work. G.A. reports personal fees, research support and travel support from Janssen during the conduct of the study; personal fees and/or travel support from Astellas, Pfizer, Millennium Pharmaceuticals, Ipsen, Ventana, Veridex, Novartis, Abbott Laboratories, ESSA Pharmaceuticals, Bayer Healthcare Pharmaceuticals, Takeda and Sanofi-Aventis and research funding from AstraZeneca, Innocrin Pharma and Arno Therapeutics outside the submitted work; in addition, G.A.?s former employer, The Institute of Cancer Research (ICR), receives royalty income from abiraterone acetate and GA receives a share of this income through ICR's Rewards to Discoverers scheme. E.M.V.A reports advisory/consulting role: Tango Therapeutics, Genome Medical, Invitae, Enara Bio, Janssen, Manifold Bio, Monte Rosa; research support: Novartis, BMS; equity: Tango Therapeutics, Genome Medical, Syapse, Enara Bio, Manifold Bio, Microsoft, Monte Rosa; travel reimbursement: Roche/Genentech; patents: Institutional patents filed on chromatin mutations and immunotherapy response, and methods for clinical interpretation. P.T.T. reported receiving grants from RefleXion Medical, the Prostate Cancer Foundation, and Movember Foundation; personal fees from Noxopharm, Janssen-Taris Biomedical, Myovant, AstraZeneca, and RefleXion; grants from Astellas and Bayer Healthcare; and owning patent No. 9114158 (with royalties from Natsar Pharmaceuticals) outside the submitted work. D.E.S reports personal fees: Janssen, AstraZeneca, Bayer, Boston Scientific, and Blue Earth; funding: Janssen. G.L. is a co-founder and chief medical officer of AIQ Solutions (Madison, WI). M.A.A. reports past consultation for Pfizer, Astellas, and Exelixis, and current research funding from Arcus, Pfizer, and Merck. C.J.S. report consulting or advisory role: Sanofi, Janssen, Astellas Pharma, Bayer, Genentech, Pfizer, Lilly; research funding: Janssen Biotech (Inst), Astellas Pharma (Inst), Sanofi (Inst), Bayer (Inst), Sotio (Inst), Dendreon (Inst); patents, royalties, other intellectual property: Pathenolide (Indiana University): dimethylaminoparthenolide (Leuchemix); Exelixis: Abiraterone plus cabozantinib combination; stock or other ownership: Leuchemix. Publisher Copyright: © 2021 The Authors

PY - 2021/9

Y1 - 2021/9

N2 - Background: The phase III CHAARTED trial established upfront androgen-deprivation therapy (ADT) plus docetaxel (D) as a standard for metastatic hormone-sensitive prostate cancer (mHSPC) based on meaningful improvement in overall survival (OS). Biological prognostic markers of outcomes and predictors of chemotherapy benefit are undefined. Patients and methods: Whole transcriptomic profiling was performed on primary PC tissue obtained from patients enrolled in CHAARTED prior to systemic therapy. We adopted an a priori analytical plan to test defined RNA signatures and their associations with HSPC clinical phenotypes and outcomes. Multivariable analyses (MVAs) were adjusted for age, Eastern Cooperative Oncology Group status, de novo metastasis presentation, volume of disease, and treatment arm. The primary endpoint was OS; the secondary endpoint was time to castration-resistant PC. Results: The analytic cohort of 160 patients demonstrated marked differences in transcriptional profile compared with localized PC, with a predominance of luminal B (50%) and basal (48%) subtypes, lower androgen receptor activity (AR-A), and high Decipher risk disease. Luminal B subtype was associated with poorer prognosis on ADT alone but benefited significantly from ADT + D [OS: hazard ratio (HR) 0.45; P = 0.007], in contrast to basal subtype which showed no OS benefit (HR 0.85; P = 0.58), even in those with high-volume disease. Higher Decipher risk and lower AR-A were significantly associated with poorer OS in MVA. In addition, higher Decipher risk showed greater improvements in OS with ADT + D (HR 0.41; P = 0.015). Conclusion: This study demonstrates the utility of transcriptomic subtyping to guide prognostication in mHSPC and potential selection of patients for chemohormonal therapy, and provides proof of concept for the possibility of biomarker-guided selection of established combination therapies in mHSPC.

AB - Background: The phase III CHAARTED trial established upfront androgen-deprivation therapy (ADT) plus docetaxel (D) as a standard for metastatic hormone-sensitive prostate cancer (mHSPC) based on meaningful improvement in overall survival (OS). Biological prognostic markers of outcomes and predictors of chemotherapy benefit are undefined. Patients and methods: Whole transcriptomic profiling was performed on primary PC tissue obtained from patients enrolled in CHAARTED prior to systemic therapy. We adopted an a priori analytical plan to test defined RNA signatures and their associations with HSPC clinical phenotypes and outcomes. Multivariable analyses (MVAs) were adjusted for age, Eastern Cooperative Oncology Group status, de novo metastasis presentation, volume of disease, and treatment arm. The primary endpoint was OS; the secondary endpoint was time to castration-resistant PC. Results: The analytic cohort of 160 patients demonstrated marked differences in transcriptional profile compared with localized PC, with a predominance of luminal B (50%) and basal (48%) subtypes, lower androgen receptor activity (AR-A), and high Decipher risk disease. Luminal B subtype was associated with poorer prognosis on ADT alone but benefited significantly from ADT + D [OS: hazard ratio (HR) 0.45; P = 0.007], in contrast to basal subtype which showed no OS benefit (HR 0.85; P = 0.58), even in those with high-volume disease. Higher Decipher risk and lower AR-A were significantly associated with poorer OS in MVA. In addition, higher Decipher risk showed greater improvements in OS with ADT + D (HR 0.41; P = 0.015). Conclusion: This study demonstrates the utility of transcriptomic subtyping to guide prognostication in mHSPC and potential selection of patients for chemohormonal therapy, and provides proof of concept for the possibility of biomarker-guided selection of established combination therapies in mHSPC.

KW - Decipher

KW - biomarker

KW - docetaxel

KW - gene expression profiling

KW - metastatic prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=85111011309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85111011309&partnerID=8YFLogxK

U2 - 10.1016/j.annonc.2021.06.003

DO - 10.1016/j.annonc.2021.06.003

M3 - Article

C2 - 34129855

AN - SCOPUS:85111011309

VL - 32

SP - 1157

EP - 1166

IS - 9

ER -

Transcriptional profiling of primary prostate tumor in metastatic hormone-sensitive prostate cancer and association with clinical outcomes: correlative analysis of the E3805 CHAARTED trial

Abstract

Bibliographical note

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UN SDGs

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