期刊
ANNALS OF ONCOLOGY
卷 32, 期 9, 页码 1157-1166出版社
ELSEVIER
DOI: 10.1016/j.annonc.2021.06.003
关键词
metastatic prostate cancer; docetaxel; Decipher; gene expression profiling; biomarker
类别
资金
- Prostate Cancer Foundation Young Investigator Award [18YOUN07]
- National Health and Medical Research Council Australia, Department of Defense Early Investigator Research Award [W81XWH2010055]
- National Institutes of Health [NIH R01 CA238020-01A1]
- U.S. Department of Defense (DOD) [W81XWH2010055] Funding Source: U.S. Department of Defense (DOD)
The study demonstrates the utility of transcriptomic subtyping for prognostication and potential selection of patients for chemohormonal therapy in mHSPC, and provides proof of concept for biomarker-guided selection of established combination therapies in mHSPC.
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 (ARA), 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 thorn 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.
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