Evidence map›Paper›PMID 33009489›Full record

ArticleProstate cancer and prostatic diseases2021

Blood-based gene expression signature associated with metastatic castrate-resistant prostate cancer patient response to abiraterone plus prednisone or enzalutamide.

Naomi B Haas, Michael J LaRiviere, Thomas H Buckingham, Yauheniya Cherkas, Karl Calara-Nielsen, Brad Foulk, Jaymala Patel, Steven Gross, Denis Smirnov, David J Vaughn and 12 more

Abstract read
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In one paragraph

Article in Prostate cancer and prostatic diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact, top 81% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 3 institutions in 1 country.

Naomi B Haas *Division of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Michael J LaRiviere *Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Thomas H BuckinghamDivision of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Yauheniya CherkasJanssen, Pharmaceutical Companies of Johnson and Johnson, Spring House, PA, USA.
Karl Calara-NielsenJanssen, Pharmaceutical Companies of Johnson and Johnson, Spring House, PA, USA.
Brad FoulkJanssen, Pharmaceutical Companies of Johnson and Johnson, Spring House, PA, USA.
Jaymala PatelJanssen, Pharmaceutical Companies of Johnson and Johnson, Spring House, PA, USA.
Steven GrossJanssen, Pharmaceutical Companies of Johnson and Johnson, Spring House, PA, USA.
Denis SmirnovJanssen, Pharmaceutical Companies of Johnson and Johnson, Spring House, PA, USA.
David J VaughnDivision of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Ravi AmaravadiDivision of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Kathryn E WellenDepartment of Cancer Biology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Samantha L SavitchDivision of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-2784-943X
Krishna J MajmundarDivision of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Taylor A BlackDivision of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Stephanie S YeeDivision of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-3469-9775
Miaoling HeDepartment of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
Eun Jeong MinDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Qi LongDepartment of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Jeremy O JonesDepartment of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
Sumanta K PalDepartment of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA, USA.
Erica L CarpenterDivision of Hematology/Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. erical@upenn.edu.ORCID http://orcid.org/0000-0002-0735-3605
University of Pennsylvania · USJohnson & Johnson (United States) · USCity of Hope · US

Funding

UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
6 · The paper itself

Abstract

backgroundPrecision medicine approaches for managing patients with metastatic castrate-resistant prostate cancer (mCRPC) are lacking. Non-invasive approaches for molecular monitoring of disease are urgently needed, especially for patients suffering from bone metastases for whom tissue biopsy is challenging. Here we utilized baseline blood samples to identify mCRPC patients most likely to benefit from abiraterone plus prednisone (AAP) or enzalutamide.

methodsBaseline blood samples were collected for circulating tumor cell (CTC) enumeration and qPCR-based gene expression analysis from 51 men with mCRPC beginning treatment with abiraterone or enzalutamide.

resultsOf 51 patients (median age 68 years [51-82]), 22 received AAP (abiraterone 1000 mg/day plus prednisone 10 mg/day) and 29 received enzalutamide (160 mg/day). The cohort was randomly divided into training (n = 37) and test (n = 14) sets. Baseline clinical variables (Gleason score, PSA, testosterone, and hemoglobin), CTC count, and qPCR-based gene expression data for 141 genes/isoforms in CTC-enriched blood were analyzed with respect to overall survival (OS). Genes with expression most associated with OS included MSLN, ARG2, FGF8, KLK3, ESRP2, NPR3, CCND1, and WNT5A. Using a Cox-elastic net model for our test set, the 8-gene expression signature had a c-index of 0.87 (95% CI [0.80, 0.94]) and was more strongly associated with OS than clinical variables or CTC count alone, or a combination of the three variables. For patients with a low-risk vs. high-risk gene expression signature, median OS was not reached vs. 18 months, respectively (HR 5.32 [1.91-14.80], p = 0.001). For the subset of 41 patients for whom progression-free survival (PFS) data was available, the median PFS for patients with a low-risk vs high-risk gene expression signature was 20 vs. 5 months, respectively (HR 2.95 [1.46-5.98], p = 0.003).

conclusionsIf validated in a larger prospective study, this test may predict patients most likely to benefit from second-generation antiandrogen therapy.

Indexed as

TranscriptomeAgedAged, 80 and overAndrogen AntagonistsAndrostenesBenzamidesBiomarkers, TumorBone NeoplasmsFollow-Up StudiesHumansLymphatic MetastasisMaleMiddle AgedNeoplastic Cells, CirculatingNitrilesPhenylthiohydantoinabirateroneAndrogen AntagonistsAndrostenesBenzamidesBiomarkers, TumorenzalutamideNitrilesPhenylthiohydantoinPrednisone

Identifiers

PMID33009489
OpenAlexW3089388888

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.