Evidence map›Paper›PMID 31564718›Full record

ReviewBritish journal of cancer2019

Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer.

Alessandro Leonetti, Sugandhi Sharma, Roberta Minari, Paola Perego, Elisa Giovannetti, Marcello Tiseo

2 registry-linked trialsOpen access · hybridAbstract readReview
In one paragraph

Review in British journal of cancer, 2019. 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. Cited by 865 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
865citing papers in PubMed, 2 pooled it
85.6field-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.

NCT06413212 recruitingnot on this mapstarted 2023, after this paper: background citation

Exploratory Study of Precise Therapy for Advanced Tumor Patients With Malignant Hydrothorax or Ascites by Using PTC Drug Sensitivity Testing

TypeobservationalSponsorLiu HuangRan2023 to 2025Enrolled55ConditionsLung Cancer, Breast Cancer, Gastric Cancer, Colorectal CancerArmsPatient-derived tumor-like cell clusters (PTC) drug sensitivity testing.
NCT07486648 phase1 / phase2not yet recruitingnot on this mapstarted 2026, after this paper: background citation

The Safety and Efficacy of Osimertinib Plus Capivasertib in EGFRm Advanced Non-small Cell Lung Cancer (NSCLC) Participants With PIK3CA/AKT1/PTEN Alterations Who Had Progressed on First-line Osimertinib Monotherapy or Plus Chemotherapy: a First-in-human, Phase Ib/Ⅱa Study (PRECISION)

TypeinterventionalSponsorShanxi Province Cancer HospitalRan2026 to 2028Enrolled53ConditionsLung Cancer (NSCLC), Lung Cancer (Non-Small Cell), Advanced Non-small-cell Lung CancerArmsCapivasertib in combination with Osimertinib
3 · Its place in the literature

Who cites it

865 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,311 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Trial
  7. Review
  8. Liquid biopsy in modern medicine: advancing diagnostics from molecular insights to clinical practice.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Review

805 more citing papers are in PubMed but not listed here.

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

6 authors at 4 institutions in 2 countries.

Alessandro LeonettiMedical Oncology Unit, University Hospital of Parma, 43126, Parma, Italy.
Sugandhi SharmaDepartment of Medical Oncology, Amsterdam University Medical Center, VU University, 1081 HV, Amsterdam, Netherlands.
Roberta MinariMedical Oncology Unit, University Hospital of Parma, 43126, Parma, Italy.
Paola PeregoMolecular Pharmacology Unit, Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133, Milan, Italy.
Elisa GiovannettiDepartment of Medical Oncology, Amsterdam University Medical Center, VU University, 1081 HV, Amsterdam, Netherlands. elisa.giovannetti@gmail.com.
Marcello TiseoMedical Oncology Unit, University Hospital of Parma, 43126, Parma, Italy.ORCID http://orcid.org/0000-0002-9204-1728
University of Parma · ITAmsterdam UMC Location Vrije Universiteit Amsterdam · NLFondazione IRCCS Istituto Nazionale dei Tumori · ITFondazione Pisa · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osimertinib is an irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that is highly selective for EGFR-activating mutations as well as the EGFR T790M mutation in patients with advanced non-small cell lung cancer (NSCLC) with EGFR oncogene addiction. Despite the documented efficacy of osimertinib in first- and second-line settings, patients inevitably develop resistance, with no further clear-cut therapeutic options to date other than chemotherapy and locally ablative therapy for selected individuals. On account of the high degree of tumour heterogeneity and adaptive cellular signalling pathways in NSCLC, the acquired osimertinib resistance is highly heterogeneous, encompassing EGFR-dependent as well as EGFR-independent mechanisms. Furthermore, data from repeat plasma genotyping analyses have highlighted differences in the frequency and preponderance of resistance mechanisms when osimertinib is administered in a front-line versus second-line setting, underlying the discrepancies in selection pressure and clonal evolution. This review summarises the molecular mechanisms of resistance to osimertinib in patients with advanced EGFR-mutated NSCLC, including MET/HER2 amplification, activation of the RAS-mitogen-activated protein kinase (MAPK) or RAS-phosphatidylinositol 3-kinase (PI3K) pathways, novel fusion events and histological/phenotypic transformation, as well as discussing the current evidence regarding potential new approaches to counteract osimertinib resistance.

Indexed as

AcrylamidesAniline CompoundsCarcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmErbB ReceptorsHumansIndolesLung NeoplasmsMutationProtein Kinase InhibitorsPyrimidinesRandomized Controlled Trials as TopicAcrylamidesAniline CompoundsEGFR protein, humanErbB ReceptorsIndolesosimertinibProtein Kinase InhibitorsPyrimidines

Identifiers

PMID31564718
PMCPMC6889286
OpenAlexW2976334328

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.