Trial reportCancer discovery2014
Dual inhibition of EGFR with afatinib and cetuximab in kinase inhibitor-resistant EGFR-mutant lung cancer with and without T790M mutations.
Trial report in Cancer discovery, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 185 papers, 1 of them a synthesis 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
185 citing papers in PubMed, 1 synthesis or guideline pooled it, 354 citations in OpenAlex.
- Oral mucositis risk with EGFR tyrosine kinase inhibitor monotherapies and combination regimens in non-small cell lung cancer: a systematic review and network meta-analysis.Frontiers in immunology · 2026Pooled it
- Trial
- Randomized Trial of Afatinib Plus Cetuximab Versus Afatinib Alone for First-Line Treatment ofJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Clonal Evolution and Heterogeneity of Osimertinib Acquired Resistance Mechanisms in EGFR Mutant Lung Cancer.Cell reports. Medicine · 2020Trial
- Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial.Nature medicine · 2019Trial
- Combination TS-1 plus EGFR-tyrosine kinase inhibitors (TKIs) for the treatment of non-small cell lung cancer after progression on first-line or further EGFR-TKIs: A phase II, single-arm trial.Thoracic cancer · 2018Trial
- Trial
- A Phase 1/2 Trial of Ruxolitinib and Erlotinib in Patients with EGFR-Mutant Lung Adenocarcinomas with Acquired Resistance to Erlotinib.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2017Trial
- Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial.Annals of oncology : official journal of the European Society for Medical Oncology · 2016Trial
- Phase I/II Study of HSP90 Inhibitor AUY922 and Erlotinib for EGFR-Mutant Lung Cancer With Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- Mechanisms and Manifestations of Ligand Bias in Signaling: Focus on Receptor Tyrosine Kinases.Chemical reviews · 2026Review
- Opportunities and challenges in the development of evolving EGFR inhibitors to overcome EGFR TKIs resistance.Acta pharmacologica Sinica · 2026Review
- Amivantamab Plus Lazertinib and Platin-Based Chemotherapy Plus Osimertinib in EGFR-Mutant NSCLC: How to Choose Among Them and When Is Monotherapy with Osimertinib Still the Best Option?Current oncology (Toronto, Ont.) · 2026Review
- Article
- Afatinib and Necitumumab inJTO clinical and research reports · 2025Article
- Histological transformation in lung adenocarcinoma: Insights of mechanisms and therapeutic windows.Journal of translational internal medicine · 2024Article
- Comprehensive mutational scanning of EGFR reveals TKI sensitivities of extracellular domain mutants.Nature communications · 2024Article
- Safety and efficacy of SNK01 (autologous natural killer cells) in combination with cytotoxic chemotherapy and/or cetuximab after failure of prior tyrosine kinase inhibitor in non-small cell lung cancer: non-clinical mouse model and phase I/IIa clinical study.Journal for immunotherapy of cancer · 2024Article
- Role of EGFR and FASN in breast cancer progression.Journal of cell communication and signaling · 2023Review
- L858R emerges as a potential biomarker predicting response of lung cancer models to anti-EGFR antibodies: Comparison of osimertinib vs. cetuximab.Cell reports. Medicine · 2023Article
125 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledEGFR-mutant lung cancers responsive to reversible EGFR inhibitors (gefitinib/erlotinib) develop acquired resistance, mediated by second-site EGFR T790M mutation in >50% of cases. Preclinically, afatinib (irreversible ErbB family blocker) plus cetuximab (anti-EGFR monoclonal antibody) overcomes T790M-mediated resistance. This phase Ib study combining afatinib and cetuximab enrolled heavily pretreated patients with advanced EGFR-mutant lung cancer and acquired resistance to erlotinib/gefitinib. Patients provided post-acquired-resistance tumor samples for profiling EGFR mutations. Among 126 patients, objective response rate (overall 29%) was comparable in T790M-positive and T790M-negative tumors (32% vs. 25%; P = 0.341). Median progression-free survival was 4.7 months (95% confidence interval, 4.3-6.4), and the median duration of confirmed objective response was 5.7 months (range, 1.8-24.4). Therapy-related grade 3/4 adverse events occurred in 44%/2% of patients. Afatinib-cetuximab demonstrated robust clinical activity and a manageable safety profile in EGFR-mutant lung cancers with acquired resistance to gefitinib or erlotinib, both with and without T790M mutations, warranting further investigation. SIGNIFICANCE: This article reports the results of a trial combining afatinib and cetuximab in patients with acquired resistance and details the first clinical proof-of-concept for the preclinical hypothesis that a significant proportion of tumors in patients with acquired resistance to gefitinib/erlotinib remain dependent on EGFR signaling for survival.
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What OpenQuestion holds
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.