Evidence map›Paper›PMID 38305868›Full record

ArticleCancer chemotherapy and pharmacology2024

UGT1A4 Polymorphism is not Associated with a Clinically Relevant Change in Giredestrant Exposure.

Vikram Malhi, Malgorzata Nowicka, Ya-Chi Chen, Priya Agarwal, Marie Waldvogel, Yi Ting Kayla Lien, Marc Hafner, Pablo Perez-Moreno, Heather M Moore, Jiajie Yu

2 registry-linked trialsOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer chemotherapy and pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
0.5field-weighted citation impact, top 41% 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.

NCT03332797 phase1active not recruitingnot on this map

A Phase Ia/Ib, Multicenter, Open-Label, Dose Escalation, Dose Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-9545 Alone or in Combination With Palbociclib and/or LHRH Agonist in Patients With Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer

TypeinterventionalSponsorGenentech, Inc.Ran2017 to 2027Enrolled181ConditionsBreast CancerArmsGDC-9545, Palbociclib, LHRH Agonist
NCT04576455 phase2active not recruitingnot on this map

A Phase II, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy and Safety of GDC-9545 Compared With Physician's Choice of Endocrine Monotherapy in Patients With Previously Treated Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

TypeinterventionalSponsorHoffmann-La RocheRan2020 to 2027Enrolled303ConditionsEstrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast CancerArmsGiredestrant, Fulvestrant or an Aromatase Inhibitor (Physician Choice), LHRH Agonist
3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

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

10 authors at 1 institution in 1 country.

Vikram MalhiDepartment of Clinical Pharmacology, Genentech, Inc., South San Francisco, CA, 650-484-6516, USA.
Malgorzata NowickaOncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA.
Ya-Chi ChenDepartment of Clinical Pharmacology, Genentech, Inc., South San Francisco, CA, 650-484-6516, USA.
Priya AgarwalDepartment of Clinical Pharmacology, Genentech, Inc., South San Francisco, CA, 650-484-6516, USA.
Marie WaldvogelProduct Development Clinical Operations, Genentech, Inc., South San Francisco, CA, USA.
Yi Ting Kayla LienDepartment of Clinical Pharmacology, Genentech, Inc., South San Francisco, CA, 650-484-6516, USA.
Marc HafnerOncology Bioinformatics, Genentech, Inc., South San Francisco, CA, USA.
Pablo Perez-MorenoProduct Development Oncology, Genentech, Inc., South San Francisco, CA, USA.
Heather M MooreOncology Biomarker Development, Genentech, Inc., South San Francisco, CA, USA.
Jiajie YuDepartment of Clinical Pharmacology, Genentech, Inc., South San Francisco, CA, 650-484-6516, USA. yuj59@gene.com.ORCID 0000-0001-6975-5047
Gene Therapy Laboratory · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeGiredestrant is a potent, orally bioavailable, small-molecule selective estrogen receptor antagonist and degrader (SERD) that is being developed for the treatment of patients with estrogen receptor (ER)-positive breast cancer. In vitro, giredestrant was primarily metabolized by UGT1A4. The goal of this study was to investigate if UGT1A4 polymorphism had a clinically relevant impact on giredestrant exposure.

methodsGenotyping and pharmacokinetic data were obtained from 118 and 61 patients in two clinical studies, GO39932 [NCT03332797] and acelERA Breast Cancer [NCT04576455], respectively.

resultsThe overall allelic frequencies of UGT1A4*2 and UGT1A4*3 were 3.3% and 11%, respectively. Giredestrant exposure was consistent between patients with wild-type UGT1A4 and UGT1A4*2 and *3 polymorphisms, with no clinically relevant difference observed. In addition, haplotype analysis indicated that no other UGT1A4 variants were significantly associated with giredestrant exposure.

conclusionTherefore, this study indicates that UGT1A4 polymorphism status is unlikely a clinically relevant factor to impact giredestrant exposure and giredestrant can be administered at the same dose level regardless of patients' UGT1A4 polymorphism status.

Indexed as

Breast NeoplasmsGlucuronosyltransferaseAdultAgedFemaleGene FrequencyGenotypeHaplotypesHumansMiddle AgedPolymorphism, Geneticbilirubin glucuronoside glucuronosyltransferaseGlucuronosyltransferaseGiredestrantPharmacokineticPolymorphismSERDUGT1A4

Identifiers

PMID38305868
PMCPMC11258046
OpenAlexW4391474197

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.