Evidence map›Paper›PMID 38229766›Full record

ArticleJTO clinical and research reports2024

The Impact of On-Target Resistance Mediated by EGFR-T790M or EGFR-C797S on EGFR Exon 20 Insertion Mutation Active Tyrosine Kinase Inhibitors.

Ikei S Kobayashi, William Shaffer, Hollis Viray, Deepa Rangachari, Paul A VanderLaan, Susumu S Kobayashi, Daniel B Costa

Open access · goldAbstract read
In one paragraph

Article in JTO clinical and research reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

7 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. Current paradigm of EGFRMed (New York, N.Y.) · 2025
    Review
  4. Article
  5. Article
  6. Article
  7. TargetingCancer control : journal of the Moffitt Cancer Center
    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

7 authors at 2 institutions in 2 countries.

Ikei S KobayashiDivision of Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
William ShafferDivision of Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Hollis VirayDivision of Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Deepa RangachariDivision of Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Paul A VanderLaanDepartment of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Susumu S KobayashiDivision of Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Daniel B CostaDivision of Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Harvard University · USBeth Israel Deaconess Medical Center · US

Funding

Unmet needs for specific subsets of EGFR mutated lung cancerR37CA218707 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI COSTA, DANIEL BOTELHO · 2018 to 2024
$2.8M
Role of KAT5 in lung cancerR01CA240257 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI KOBAYASHI, SUSUMU · 2020 to 2024
$2.0M
NCI NIH HHS R01 CA240257NCI NIH HHS R37 CA218707
6 · The paper itself

Abstract

Introduction: Mechanisms of resistance to EGFR exon 20 insertion mutation active inhibitors have not been extensively studied in either robust preclinical models or patient-derived rebiopsy specimens. We sought to characterize on-target resistance mutations identified in Methods: We identified mechanisms of resistance to EGFR exon 20 insertion mutation active inhibitors and then used preclinical models of EGFR exon 20 insertion mutations (A767_V769dupASV, D770_N771insSVD, V773_C774insH) plus common EGFR mutants to probe inhibitors in the absence/presence of EGFR-T790M or EGFR-C797S. Results: Mobocertinib had a favorable therapeutic window in relation to EGFR wild type for EGFR exon 20 insertion mutants, but the addition of EGFR-T790M or EGFR-C797S negated the observed window. Zipalertinib had a favorable therapeutic window for cells driven by EGFR-A767_V769dupASV or EGFR-D770_N771insSVD in the presence or absence of EGFR-T790M. Furmonertinib and sunvozertinib had the most favorable therapeutic windows in the presence or absence of EGFR-T790M in all cells tested. Conclusions: This report highlights that poziotinib and mobocertinib are susceptible to on-target resistance mediated by

Indexed as

EGFR-C797SEGFR-T790MFurmonertinibMobocertinibSunvozertinibZipalertinib

Identifiers

PMID38229766
PMCPMC10788275
OpenAlexW4389043715

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.