Evidence map›Paper›PMID 33641211›Full record

ArticleThe oncologist2021

Phase Ib Study of the Oral Proteasome Inhibitor Ixazomib (MLN9708) and Fulvestrant in Advanced ER+ Breast Cancer Progressing on Fulvestrant.

Gary Schwartz, Kevin Shee, Bianca Romo, Jonathan Marotti, Alexei Kisselev, Lionel Lewis, Todd Miller

Open access · bronzeAbstract readClinical Trial, Phase I
In one paragraph

Article in The oncologist, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.4field-weighted citation impact, top 42% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

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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

7 authors at 2 institutions in 1 country.

Gary SchwartzGeisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Kevin SheeGeisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Bianca RomoGeisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Jonathan MarottiGeisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Alexei KisselevAuburn University, Auburn, Alabama, USA.
Lionel LewisGeisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Todd MillerGeisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
Dartmouth College · USAuburn University · US

Funding

Proteasome inhibitors for the treatment of solid tumorsR01CA213223 · NCI · AUBURN UNIVERSITY AT AUBURN · PI KISSELEV, ALEXEI · 2017 to 2021
$1.8M
Olympus FV1200 Near Infrared Confocal MicroscopeS10OD021616 · OD · DARTMOUTH COLLEGE · PI STAN, RADU VIRGIL · 2016 to 2016
$321k
Microenvironmental FGF2-mediated resistance to anti-estrogen and PI3K/mTOR pathway therapeutics in ER+ breast cancerF30CA216966 · NCI · DARTMOUTH COLLEGE · PI SHEE, KEVIN · 2017 to 2020
$176k
NCI NIH HHS F30 CA216966NCI NIH HHS R01 CA213223NIH HHS S10 OD021616
6 · The paper itself

Abstract

lessons learnedFulvestrant is a selective estrogen receptor (ER)-downregulating antiestrogen that blocks ER transcriptional activity and is approved for ER-positive breast cancer. Fulvestrant also induces accumulation of insoluble ER and activates an unfolded protein response; proteasome inhibitors have been shown to enhance these effects in preclinical models.

backgroundFulvestrant is a selective estrogen receptor (ER)-downregulating antiestrogen that blocks ER transcriptional activity and is approved for ER-positive (+) breast cancer. Fulvestrant also induces accumulation of insoluble ER and activates an unfolded protein response; proteasome inhibitors have been shown to enhance these effects in preclinical models.

methodsThis is a single-center phase Ib study with a 3+3 design of fulvestrant and the proteasome inhibitor ixazomib (MLN9708) in patients with advanced ER+ breast cancer that was progressing on fulvestrant. A dose-escalation design allowed establishment of the ixazomib maximum tolerated dose (MTD). Secondary objectives included progression-free survival, pharmacokinetics, and tumor molecular analyses.

resultsAmong nine evaluable subjects, treatment was well-tolerated without dose-limiting toxicities The MTD of ixazomib was 4 mg in combination with fulvestrant. Plasma concentrations of the active form of ixazomib (MLN2238) in the 4-mg dose cohort had a median (range) maximal concentration (C

conclusionThis drug combination has a favorable safety profile and antitumor activity in patients with fulvestrant-resistant advanced ER+ breast cancer that justifies future testing.

Indexed as

Breast NeoplasmsProteasome InhibitorsAntineoplastic Agents, HormonalBoron CompoundsEstradiolFemaleFulvestrantGlycineHumansReceptors, EstrogenAntineoplastic Agents, HormonalBoron CompoundsEstradiolFulvestrantGlycineixazomibProteasome InhibitorsReceptors, EstrogenAnti-estrogenBreast cancerEndocrine therapyProteasome inhibitor

Identifiers

PMID33641211
PMCPMC8176977
OpenAlexW3135389008

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

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.