Hamid, AA;
Huang, H-C;
Wang, V;
Chen, Y-H;
Feng, F;
Den, R;
Attard, G;
... Sweeney, CJ; + view all
(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)
pp. 1157-1166.
10.1016/j.annonc.2021.06.003.
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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.
| Type: | Article |
|---|---|
| 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 |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.annonc.2021.06.003 |
| Publisher version: | https://doi.org/10.1016/j.annonc.2021.06.003 |
| Language: | English |
| Additional information: | © 2021 Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Decipher, biomarker, docetaxel, gene expression profiling, metastatic prostate cancer |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10133017 |
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