ArticleNature medicine2018
Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 262 papers, 4 of them syntheses that pooled 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.
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.
Who cites it
262 citing papers in PubMed, 4 syntheses or guidelines pooled it, 447 citations in OpenAlex.
- Cost-effectiveness analyses of amivantamab plus lazertinib and lazertinib versus osimertinib in non-small cell lung cancer with EGFR mutations.Frontiers in pharmacology · 2025Pooled it
- Poziotinib in non-small-cell lung cancer patients with HER2 exon 20 mutations: A pooled analysis of randomized clinical trials.Medicine · 2022Pooled it
- Efficacy of targeted therapy in patients with HER2-positive non-small cell lung cancer: A systematic review and meta-analysis.British journal of clinical pharmacology · 2022Pooled it
- Therapeutic exploration of uncommon EGFR exon 20 insertion mutations in advanced non-small cell lung cancer: breaking through brambles and thorns.Journal of cancer research and clinical oncology · 2022Pooled it
- Efficacy of Neratinib-Based Therapy in ERBB2-Mutant Lung Adenocarcinomas: Findings From 2 International Phase 2 Studies.Clinical lung cancer · 2026Trial
- Poziotinib for EGFR exon 20-insertion NSCLC: Clinical efficacy of the phase 2 ZENITH trial and differential impact of EGFR exon 20 insertion location on sensitivity.Nature communications · 2025Trial
- Poziotinib in Treatment-Naive NSCLC Harboring HER2 Exon 20 Mutations: ZENITH20-4, A Multicenter, Multicohort, Open-Label, Phase 2 Trial (Cohort 4).Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023Trial
- Poziotinib for EGFR exon 20-mutant NSCLC: Clinical efficacy, resistance mechanisms, and impact of insertion location on drug sensitivity.Cancer cell · 2022Trial
- Poziotinib for Patients WithJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- Poziotinib in Non-Small-Cell Lung Cancer HarboringJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- Erlotinib and Onalespib Lactate Focused on EGFR Exon 20 Insertion Non-Small Cell Lung Cancer (NSCLC): A California Cancer Consortium Phase I/II Trial (NCI 9878).Clinical lung cancer · 2021Trial
- Activity and Safety of Mobocertinib (TAK-788) in Previously Treated Non-Small Cell Lung Cancer withCancer discovery · 2021Trial
- Recent advances in HER2-targeted inhibitors for cancer therapy.Pharmaceutical science advances · 2026Review
- New Treatment Strategies for Rare Genomic Alterations:Cancers · 2026Review
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Opportunities and challenges in the development of evolving EGFR inhibitors to overcome EGFR TKIs resistance.Acta pharmacologica Sinica · 2026Review
- Design and development of novel EGFR inhibitors spanning all subgroups of EGFR mutations in non-small cell lung cancer.Innovation (Cambridge (Mass.)) · 2026Article
- Loss of Payload Sensitivity and Other Mechanisms of Resistance to T-DXd in HER2-Mutant NSCLC: Implications for Subsequent Responsiveness to HER2 TKIs.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Evaluating zongertinib in the treatment of patients with HER2-mutant non-small cell lung cancer.Future oncology (London, England) · 2026Review
- Therapeutic Advances in Non-Small Cell Lung Cancer HarboringInternational journal of molecular sciences · 2026Review
202 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
24 authors at 7 institutions in 1 country.
Funding
Abstract
Although most activating mutations of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancers (NSCLCs) are sensitive to available EGFR tyrosine kinase inhibitors (TKIs), a subset with alterations in exon 20 of EGFR and HER2 are intrinsically resistant and lack an effective therapy. We used in silico, in vitro, and in vivo testing to model structural alterations induced by exon 20 mutations and to identify effective inhibitors. 3D modeling indicated alterations restricted the size of the drug-binding pocket, limiting the binding of large, rigid inhibitors. We found that poziotinib, owing to its small size and flexibility, can circumvent these steric changes and is a potent inhibitor of the most common EGFR and HER2 exon 20 mutants. Poziotinib demonstrated greater activity than approved EGFR TKIs in vitro and in patient-derived xenograft models of EGFR or HER2 exon 20 mutant NSCLC and in genetically engineered mouse models of NSCLC. In a phase 2 trial, the first 11 patients with NSCLC with EGFR exon 20 mutations receiving poziotinib had a confirmed objective response rate of 64%. These data identify poziotinib as a potent, clinically active inhibitor of EGFR and HER2 exon 20 mutations and illuminate the molecular features of TKIs that may circumvent steric changes induced by these mutations.
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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.