Evidence map›Paper›PMID 36401732›Full record

ArticleBreast cancer research and treatment2023

The oral selective estrogen receptor degrader GDC-0810 (ARN-810) in postmenopausal women with hormone receptor-positive HER2-negative (HR + /HER2 -) advanced/metastatic breast cancer.

Aditya Bardia, Ingrid Mayer, Eric Winer, Hannah M Linden, Cynthia X Ma, Barbara A Parker, Meritxell Bellet, Carlos L Arteaga, Sravanthi Cheeti, Mary Gates and 9 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Breast cancer research and treatment, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01823835 (An Open-Label, Phase Ia/Ib/IIa Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or an LHRH Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer), which is not on this map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.0field-weighted citation impact, top 7% 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.

NCT01823835 phase1 / phase2terminatednot on this map

An Open-Label, Phase Ia/Ib/IIa Study of GDC-0810 Single Agent or in Combination With Palbociclib and/or an LHRH Agonist in Women With Locally Advanced or Metastatic Estrogen Receptor Positive Breast Cancer

TypeinterventionalSponsorGenentech, Inc.Ran2014 to 2020Enrolled152ConditionsBreast CancerArmsGDC-0810, LHRH Agonist, Palbociclib
3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Targeting Estrogen Receptor for Breast Cancer.Current issues in molecular biology · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. An Open-label Phase I Study of GDC-0927 in Postmenopausal Women with Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
    Article
  12. Clinical application of circulating tumor DNA in breast cancer.Journal of cancer research and clinical oncology · 2021
    Review
  13. Review
  14. 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

19 authors at 10 institutions in 2 countries.

Aditya BardiaMassachusetts General Hospital Cancer Center, Harvard Medical School, Bartlett Hall Extension 237, 55 Fruit St, Boston, MA, 02114, USA. bardia.aditya@mgh.harvard.edu.ORCID http://orcid.org/0000-0003-4885-1157
Ingrid MayerVanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Eric WinerDana-Farber Cancer Institute, Boston, MA, USA.
Hannah M LindenUniversity of Washington, Seattle, WA, USA.
Cynthia X MaWashington University School of Medicine, St. Louis, MO, USA.
Barbara A ParkerUniversity of California San Diego Moores Cancer Center, San Diego, CA, USA.
Meritxell BelletVall d'Hebron Institute of Oncology, Barcelona, Spain.
Carlos L ArteagaUT Southwestern Simmons Comprehensive Cancer Center, Dallas, TX, USA.
Sravanthi CheetiGenentech, Inc, South San Francisco, CA, USA.
Mary GatesGenentech, Inc, South San Francisco, CA, USA.
Ching-Wei ChangGenentech, Inc, South San Francisco, CA, USA.
Jill FredricksonGenentech, Inc, South San Francisco, CA, USA.
Jill M SpoerkeGenentech, Inc, South San Francisco, CA, USA.
Heather M MooreGenentech, Inc, South San Francisco, CA, USA.
Jennifer GiltnaneGenentech, Inc, South San Francisco, CA, USA.
Lori S FriedmanGenentech, Inc, South San Francisco, CA, USA.
Edna Chow ManevalORIC Pharmaceuticals, South San Francisco, CA, USA.
Iris ChanGenentech, Inc, South San Francisco, CA, USA.
Komal JhaveriMemorial Sloan Kettering Cancer Center, New York, Weill Cornell Medical College, New York, NY, USA.
Sunesis (United States) · USHarvard University · USMemorial Sloan Kettering Cancer Center · USSouthwestern Medical Center · USUniversity of California San Diego · USUniversity of Washington · USVall d'Hebron Institute of Oncology · ESVanderbilt University · USWashington University in St. Louis · USYale Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

purposeGDC-0810 (ARN-810) is a novel, non-steroidal, orally bioavailable, selective estrogen receptor degrader (SERD) that potentially inhibits ligand-dependent and ligand-independent estrogen receptor (ER)-mediated signaling.

methodsA phase Ia/Ib/IIa dose escalation, combination treatment with palbociclib or a luteinizing hormone-releasing hormone, and expansion study determined the safety, pharmacokinetics, and recommended phase 2 dose (RP2D) of GDC-0810 in postmenopausal women with ER + (HER2 -) locally advanced or metastatic breast cancer (MBC). Baseline plasma ctDNA samples were analyzed to determine the ESR1 mutation status.

resultsPatients (N = 152) received GDC-0810 100-800 mg once daily (QD) or 300-400 mg twice daily, in dose escalation, expansion, as single agent or combination treatment. Common adverse events regardless of attribution to study drug were diarrhea, nausea, fatigue, vomiting, and constipation. There was one dose-limiting toxicity during dose escalation. The maximum tolerated dose was not reached. GDC-0810 600 mg QD taken with food was the RP2D. Pharmacokinetics were predictable. FES reduction (> 90%) highlighting pharmacodynamic engagement of ER was observed. Outcomes for the overall population and for patients with tumors harboring ESR1 mutations included partial responses (4% overall; 4% ESR1), stable disease (39% overall; 42% ESR1), non-complete response/non-progressive disease (13% overall; 12% ESR1), progressive disease (40% overall; 38% ESR1), and missing/unevaluable (5% overall; 5% ESR1). Clinical benefit (responses or SD, lasting ≥ 24 weeks) was observed in patients in dose escalation (n = 16, 39%) and expansion (n = 24, 22%).

conclusionGDC-0810 was safe and tolerable with preliminary anti-tumor activity in heavily pretreated patients with ER + advanced/MBC, with/without ESR1 mutations, highlighting the potential for oral SERDs. Clinical Trial and registration date April 4, 2013. NCT01823835 .

Indexed as

Breast NeoplasmsAntineoplastic Combined Chemotherapy ProtocolsCinnamatesErb-b2 Receptor Tyrosine KinasesEstrogen AntagonistsFemaleHumansIndazolesLigandsPostmenopauseReceptors, Estrogen3-(4-(2-(2-chloro-4-fluorophenyl)-1-(1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylic acidCinnamatesErb-b2 Receptor Tyrosine KinasesEstrogen AntagonistsIndazolesLigandsReceptors, EstrogenGDC-0810; HR +HER2 −Metastatic breast cancerPhase 1PostmenopausalSelective estrogen receptor degrader

Identifiers

PMID36401732
PMCPMC9823088
OpenAlexW4309391099

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.