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Lung cancers with a mutated EGFR gene are treated with EGFR pills, but which pill and how well it works depends on exactly where the mutation is. Exon 19 deletions and L858R are the 'classic' sensitive ones; exon 20 insertions resist most pills; T790M and C797S appear when resistance develops.
EGFR mutations occur in about 15% of Western and 40-50% of East Asian lung adenocarcinomas, mostly in never-smokers. Exon 19 deletions (best outcomes) and L858R respond to osimertinib, now standard first line (FLAURA) and adjuvant (ADAURA), with amivantamab-lazertinib (MARIPOSA) or osimertinib plus chemotherapy (FLAURA2) as intensified options. Exon 20 insertions need amivantamab or sunvozertinib. T790M was the resistance mutation to first-generation TKIs that osimertinib overcame; C797S and MET amplification are the main escape routes from osimertinib. Testing is by tissue NGS or plasma ctDNA at diagnosis and at progression.
In plain words · A growth receptor that is mutated in some lung cancers and overproduced in others; the first great success of targeted pills.
Showing the target this term concerns: EGFR.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
Lung cancer in never-smokers is not smokers' lung cancer with the smoking removed; it is a different set of diseases with a different clock. The slow-growing piano subtype in particular is the argument that a screening test aimed at never-smokers would need to look for something other than what low-dose computed tomography was built to find.
It shows that the driver frequencies quoted in Western guidelines are population statistics rather than facts about the disease, which matters for how many patients anywhere are expected to benefit from a given medicine.
It changed how resistance is investigated: the first question at progression on osimertinib is whether T790M is still there, because losing it means the tumour is no longer EGFR-driven in the growing compartment and another EGFR inhibitor will not help.
It is the document that defines what a complete lung cancer molecular report looks like, and its asymmetry about plasma, rule in but never rule out, is the single most useful sentence in it.
One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
It generalised the single-patient finding and made the point that drug-resistant subclones are selected by treatment rather than created by it, which is the model the whole field now works with.
Resistance to a targeted drug usually has a cause you can read off a sequence, which means it can be targeted in turn. Osimertinib exists because of this paper.
Shares LUX-Lung 3, EGFR L858R, EGFR exon 19 deletion, Gefitinib.
Shares EGFR L858R, EGFR T790M, EGFR exon 19 deletion, Erlotinib.
Shares LUX-Lung 3, Gefitinib, Erlotinib, Tyrosine kinase inhibitor (TKI).
Shares EGFR mutation and resistance of non-small-cell lung cancer to gefitinib, Gefitinib, Erlotinib, Driver mutation.
Shares LUX-Lung 3, Gefitinib, Tyrosine kinase inhibitor (TKI), EGFR-mutated non-small-cell lung cancer.
Shares EGFR T790M, EGFR mutation and resistance of non-small-cell lung cancer to gefitinib, Gefitinib, Erlotinib.
Shares EGFR exon 20 insertion, Sunvozertinib, EGFR-mutated non-small-cell lung cancer, EGFR.
Shares On-target resistance mutations (gatekeeper, solvent-front, compound), Tyrosine kinase inhibitor (TKI), Osimertinib, EGFR-mutated non-small-cell lung cancer.