Evidence map›Paper›PMID 30462160›Full record

ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2019

Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge.

C M Parseghian, J M Loree, V K Morris, X Liu, K K Clifton, S Napolitano, J T Henry, A A Pereira, E Vilar, B Johnson and 14 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.

0numbers the graph read from it
0cells of the map it votes in
135citing papers in PubMed
9.1field-weighted citation impact, top 1% 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

135 citing papers in PubMed, 233 citations in OpenAlex.

  1. Trial
  2. Amivantamab Monotherapy in ChemorefractoryJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
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  9. Expanded Low Allele FrequencyClinical cancer research : an official journal of the American Association for Cancer Research · 2021
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75 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 4 institutions in 1 country.

C M ParseghianDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: cparseghian@mdanderson.org.
J M LoreeBC Cancer, Vancouver, Canada.
V K MorrisDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
X LiuDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA.
K K CliftonDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
S NapolitanoDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
J T HenryDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
A A PereiraDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
E VilarDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Division of Cancer Prevention and Population Sciences, Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, USA.
B JohnsonDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
B KeeDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
K RaghavDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
A DasariDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
J WuDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
N GargDivision of Diagnostic Imaging, Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, USA.
V M RaymondGuardant Health Inc, Redwood City, USA.
K C BanksGuardant Health Inc, Redwood City, USA.
A A TalasazGuardant Health Inc, Redwood City, USA.
R B LanmanGuardant Health Inc, Redwood City, USA.
J H StricklerDuke University Medical Center, Durham, USA.
D S HongDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA.
R B CorcoranMassachusetts General Hospital Cancer Center, Boston, USA; Department of Medicine, Harvard Medical School, Boston, USA.
M J OvermanDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
S KopetzDivision of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
The University of Texas MD Anderson Cancer Center · USGuardant (United States) · USDuke Medical Center · USHarvard University · US

Funding

Paul Calabresi Clinical Oncology AwardK12CA088084 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI David S. Hong, Scott Kopetz · 2000 to 2026
$14.0M
Project 3: Inhibiting Oxidative Phosphorylation in Pancreatic CancerP50CA221707 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KOPETZ, SCOTT · 2019 to 2023
$11.0M
TRAINING FOR ACADEMIC ONCOLOGY/HEMATOLOGYT32CA009666 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Michael Davies, Courtney DiNardo · 1994 to 2026
$9.8M
Center for Clinical and Translational Sciences (CCTS)KL2TR000370 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2012 to 2016
$4.3M
Therapeutic Strategies for Patients With BRAF Mutant Colorectal CancerR01CA187238 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HONG, DAVID S., KOPETZ, SCOTT · 2014 to 2018
$1.7M
NCATS NIH HHS KL2 TR000370NCI NIH HHS P50 CA221707NCI NIH HHS R01 CA187238NCI NIH HHS T32 CA009666
6 · The paper itself

Abstract

backgroundColorectal cancer (CRC) has been shown to acquire RAS and EGFR ectodomain mutations as mechanisms of resistance to epidermal growth factor receptor (EGFR) inhibition (anti-EGFR). After anti-EGFR withdrawal, RAS and EGFR mutant clones lack a growth advantage relative to other clones and decay; however, the kinetics of decay remain unclear. We sought to determine the kinetics of acquired RAS/EGFR mutations after discontinuation of anti-EGFR therapy. PATIENTS AND

methodsWe present the post-progression circulating tumor DNA (ctDNA) profiles of 135 patients with RAS/BRAF wild-type metastatic CRC treated with anti-EGFR who acquired RAS and/or EGFR mutations during therapy. Our validation cohort consisted of an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling. A separate retrospective cohort of 80 patients was used to evaluate overall response rate and progression free survival during re-challenge therapies.

resultsOur analysis showed that RAS and EGFR relative mutant allele frequency decays exponentially (r2=0.93 for RAS; r2=0.94 for EGFR) with a cumulative half-life of 4.4 months. We validated our findings using an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling, confirming exponential decay with an estimated half-life of 4.3 months. A separate retrospective cohort of 80 patients showed that patients had a higher overall response rate during re-challenge therapies after increasing time intervals, as predicted by our model.

conclusionThese results provide scientific support for anti-EGFR re-challenge and guide the optimal timing of re-challenge initiation.

Indexed as

Drug Resistance, NeoplasmColorectal NeoplasmsDisease ProgressionErbB ReceptorsFollow-Up StudiesHumansMutationNeoplasm MetastasisNeoplastic Cells, CirculatingPrognosisProtein Kinase Inhibitorsras ProteinsRetrospective StudiesSurvival RateEGFR protein, humanErbB ReceptorsProtein Kinase Inhibitorsras Proteinsanti-EGFR therapycirculating tumor DNAclonal decaycolorectal cancer

Identifiers

PMID30462160
PMCPMC6657008
OpenAlexW2901367407

What OpenQuestion holds

Textmetadata
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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.