PMID- 34716049
OWN - NLM
STAT- MEDLINE
DCOM- 20220418
LR  - 20220429
IS  - 1873-7560 (Electronic)
IS  - 0302-2838 (Linking)
VI  - 81
IP  - 1
DP  - 2022 Jan
TI  - Predictive Genomic Biomarkers of Hormonal Therapy Versus Chemotherapy Benefit in 
      Metastatic Castration-resistant Prostate Cancer.
PG  - 37-47
LID - S0302-2838(21)02060-1 [pii]
LID - 10.1016/j.eururo.2021.09.030 [doi]
AB  - BACKGROUND: Biomarkers predicting second-generation novel hormonal therapy (NHT) 
      benefit relative to taxanes are critical for optimized treatment decisions for 
      metastatic castration-resistant prostate cancer (mCRPC) patients. These 
      associations have not been reported simultaneously for common mCRPC genomic 
      biomarkers. OBJECTIVE: To evaluate predictive associations of common genomic 
      aberrations in mCRPC using an established comprehensive genomic profiling (CGP) 
      system. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study used data 
      from a deidentified US-based clinicogenomic database comprising patients treated 
      in routine clinical practice between 2011 and 2020, evaluated with Foundation 
      Medicine CGP in tissue biopsies obtained around the time of treatment decision. 
      The main cohort included 180 NHT and 179 taxane lines of therapy (LOTs) from 308 
      unique patients. The sequential cohort comprised a subset of the main cohort NHT 
      LOTs immediately followed by taxane from 55 unique patients. OUTCOME MEASUREMENTS 
      AND STATISTICAL ANALYSIS: Prostate-specific antigen (PSA) response, time to next 
      treatment (TTNT), and overall survival (OS) were assessed. Main cohort analyses 
      were adjusted for known treatment assignment biases via inverse probability of 
      treatment weighting (IPTW) in treatment interaction models. RESULTS AND 
      LIMITATIONS: In the main cohort, patients with AR amplification (ARamp) or PTEN 
      aberrations (PTENalt) had worse relative PSA response on NHT versus taxanes 
      compared with patients without. Patients with ARamp, PTENalt, or RB1 aberrations 
      (RB1alt) also had worse relative TTNT and OS on NHT but not on taxanes. In 
      multivariable models for TTNT and OS adjusted via IPTW, ARamp, PTENalt, and 
      RB1alt were shown as poor prognostic factors overall and demonstrated significant 
      treatment interactions, indicating reduced hazards of therapy switch and death on 
      taxanes versus NHT. Consistent associations favoring increased benefit from 
      subsequent taxane despite prior NHT treatment line were observed only for ARamp 
      in the sequential cohort, in which very few patients had RB1alt for assessment. 
      CONCLUSIONS: ARamp status is a candidate biomarker to predict poor effectiveness 
      of NHT relative to taxanes in mCRPC in scenarios where both options are 
      considered. PATIENT SUMMARY: Specific alterations in the DNA of tumors may assist 
      in choosing between novel oral hormonal therapies and standard chemotherapy in 
      advanced prostate cancer patients.
CI  - Copyright (c) 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Graf, Ryon P
AU  - Graf RP
AD  - Foundation Medicine, Cambridge, MA, USA. Electronic address: 
      rgraf@foundationmedicine.com.
FAU - Fisher, Virginia
AU  - Fisher V
AD  - Foundation Medicine, Cambridge, MA, USA.
FAU - Mateo, Joaquin
AU  - Mateo J
AD  - Vall d'Hebron Institute of Oncology (VHIO) and Vall d'Hebron University Hospital, 
      Barcelona, Spain.
FAU - Gjoerup, Ole V
AU  - Gjoerup OV
AD  - Foundation Medicine, Cambridge, MA, USA.
FAU - Madison, Russell W
AU  - Madison RW
AD  - Foundation Medicine, Cambridge, MA, USA.
FAU - Raskina, Kira
AU  - Raskina K
AD  - Foundation Medicine, Cambridge, MA, USA.
FAU - Tukachinsky, Hanna
AU  - Tukachinsky H
AD  - Foundation Medicine, Cambridge, MA, USA.
FAU - Creeden, James
AU  - Creeden J
AD  - Foundation Medicine, Cambridge, MA, USA.
FAU - Cunningham, Rachel
AU  - Cunningham R
AD  - Foundation Medicine, Cambridge, MA, USA.
FAU - Huang, Richard S P
AU  - Huang RSP
AD  - Foundation Medicine, Cambridge, MA, USA.
FAU - Mata, Douglas A
AU  - Mata DA
AD  - Foundation Medicine, Cambridge, MA, USA.
FAU - Ross, Jeffrey S
AU  - Ross JS
AD  - Foundation Medicine, Cambridge, MA, USA.
FAU - Oxnard, Geoffrey R
AU  - Oxnard GR
AD  - Foundation Medicine, Cambridge, MA, USA.
FAU - Venstrom, Jeffrey M
AU  - Venstrom JM
AD  - Foundation Medicine, Cambridge, MA, USA.
FAU - Zurita, Amado J
AU  - Zurita AJ
AD  - Department of Genitourinary Medical Oncology, The University of Texas MD Anderson 
      Cancer Center, Houston, TX, USA. Electronic address: azurita@mdanderson.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211026
PL  - Switzerland
TA  - Eur Urol
JT  - European urology
JID - 7512719
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Taxoids)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
SB  - IM
CIN - Eur Urol. 2022 Jan;81(1):48-49. PMID: 34742584
MH  - Biomarkers, Tumor/genetics
MH  - Humans
MH  - Male
MH  - Prostate-Specific Antigen
MH  - *Prostatic Neoplasms, Castration-Resistant/drug therapy/genetics/pathology
MH  - Retrospective Studies
MH  - Taxoids/therapeutic use
MH  - Treatment Outcome
OTO - NOTNLM
OT  - *Drug development
OT  - *Predictive biomarkers
OT  - *Propensity
OT  - *Prostate cancer
OT  - *Real world
EDAT- 2021/10/31 06:00
MHDA- 2022/04/19 06:00
CRDT- 2021/10/30 05:34
PHST- 2021/04/21 00:00 [received]
PHST- 2021/09/29 00:00 [accepted]
PHST- 2021/10/31 06:00 [pubmed]
PHST- 2022/04/19 06:00 [medline]
PHST- 2021/10/30 05:34 [entrez]
AID - S0302-2838(21)02060-1 [pii]
AID - 10.1016/j.eururo.2021.09.030 [doi]
PST - ppublish
SO  - Eur Urol. 2022 Jan;81(1):37-47. doi: 10.1016/j.eururo.2021.09.030. Epub 2021 Oct 
      26.