# EGFR T790M

Source: https://onco.cc/biomarkers/egfr-t790m/  
OnCo record `egfr-t790m` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

T790M is the gatekeeper mutation that lung cancers acquire to escape first- and second-generation EGFR inhibitors. Finding it, in tissue or blood, is the historic gate for osimertinib after an earlier EGFR drug.

## Summary

The c.2369C>T (T790M) substitution in exon 20 enlarges the ATP-binding pocket's affinity for ATP and confers resistance to erlotinib, gefitinib and afatinib; it arose in about half of patients progressing on those drugs. Osimertinib's 2015 accelerated approval (AURA) was for metastatic EGFR T790M-positive NSCLC after an EGFR TKI, detected by the cobas EGFR Mutation Test v2 in tissue or plasma, the first plasma companion diagnostic. That indication remains on the label, though first-line osimertinib has made acquired T790M uncommon. FoundationOne CDx and Guardant360 CDx also list T790M in their EGFR claims.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: T790M; EGFR T790M mutation; gatekeeper mutation EGFR; EGFR exon 20 T790M
- Tags: biomarker; egfr; resistance

## Notes

- Lung cancer: the gatekeeper substitution, found in 98 of 155 rebiopsies after a first-generation inhibitor, 63% (Yu 2013), and first described in one patient who relapsed after two years of remission (Kobayashi 2005) and independently in progressing tumours that had not carried it before treatment (Pao 2005). The guideline requires an assay sensitive to 5% allele fraction for this call (Lindeman 2018). At the next progression the question reverses: T790M was retained in only 32% of tumours resistant to osimertinib, and losing it predicted earlier progression (6.1 against 15.2 months) and a heterogeneous set of competing mechanisms (Oxnard 2018).

## Sources

- TAGRISSO prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e81b4a7-b971-45e1-9c31-29cea8c87ce7

## Connected records

- biomarkers: [EGFR C797S (and its phase with T790M)](https://onco.cc/biomarkers/egfr-c797s/), [EGFR exon 19 deletion](https://onco.cc/biomarkers/egfr-exon-19-deletion/), [EGFR L858R](https://onco.cc/biomarkers/egfr-l858r/), [MET amplification (gene copy number)](https://onco.cc/biomarkers/met-amplification-readout/)
- cancers: [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/)
- drugs: [cobas EGFR Mutation Test v2](https://onco.cc/drugs/cobas-egfr-mutation-test/), [Osimertinib](https://onco.cc/drugs/osimertinib/)
- terms: [EGFR C797S](https://onco.cc/terms/c797s/), [EGFR mutation subtypes (exon 19 deletion, L858R, exon 20 insertion, T790M)](https://onco.cc/terms/egfr-mutation-subtypes/), [On-target resistance mutations (gatekeeper, solvent-front, compound)](https://onco.cc/terms/gatekeeper-mutation/)
- key papers: [Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M](https://onco.cc/key-papers/paper-thress-nat-med/), [Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain](https://onco.cc/key-papers/paper-pao-egfr-t790m-acquired-resistance-plos-med-2005/), [Analysis of tumor specimens at the time of acquired resistance to EGFR-TKI therapy in 155 patients with EGFR-mutant lung cancers](https://onco.cc/key-papers/paper-yu-acquired-resistance-rebiopsy-egfr-ccr-2013/), [Assessment of resistance mechanisms and clinical implications in patients with EGFR T790M-positive lung cancer and acquired resistance to osimertinib](https://onco.cc/key-papers/paper-oxnard-osimertinib-resistance-mechanisms-jama-oncol-2018/), [EGFR mutation and resistance of non-small-cell lung cancer to gefitinib](https://onco.cc/key-papers/paper-kobayashi-egfr-t790m-gefitinib-resistance-nejm-2005/), [EGFR-mutant adenocarcinomas that transform to small-cell lung cancer and other neuroendocrine carcinomas: clinical outcomes](https://onco.cc/key-papers/paper-marcoux-egfr-small-cell-transformation-outcomes-jco-2019/), [Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors](https://onco.cc/key-papers/paper-sequist-genotypic-histological-evolution-egfr-resistance-sci-transl-med-2011/), [Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors](https://onco.cc/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/)
- targets: [EGFR](https://onco.cc/targets/egfr/)

---
JSON: https://onco.cc/api/v1/entities/egfr-t790m.json