EGFR Exon 19 Deletion and L858R Explained (Tagrisso Context)

Tagrisso (osimertinib) is approved for lung cancers with particular EGFR mutations, which is why searches like “EGFR exon 19 deletion Tagrisso” and “Tagrisso EGFR mutation” are so common. This guide explains what those mutation names mean, how often they occur, how they are detected in general terms, and which approved drugs are labeled for which mutation group. It is a reference summary of FDA labels and published data, not guidance on what anyone should take.

Updated November 4, 2026.

What is an EGFR mutation in lung cancer?

EGFR is a growth-signaling receptor. In a subset of non-small cell lung cancers (NSCLC), a change in the EGFR gene keeps it signaling. The afatinib label describes such non-resistant kinase-domain mutations as increasing receptor autophosphorylation and notes that exon 21 L858R substitutions and exon 19 deletions are the most commonly found (DailyMed, Gilotrif label). How Tagrisso acts on them is covered in how Tagrisso works.

Exon 19 deletions and L858R: the “common” mutations

An exon 19 deletion removes a short stretch of the gene; L858R is a single amino acid substitution in exon 21. A 2022 literature review and meta-analysis in Targeted Oncology states that these two together make up about 85% of EGFR mutations, with the remaining 10-15% being uncommon types. In the same paper, EGFR mutations were estimated in 12.5% of any-stage NSCLC and 14.8% of advanced or metastatic NSCLC in Europe, and the authors cite rates that are higher in Asian patients (38.8%) than in Caucasian patients (17.4%) (Van Sanden et al., Target Oncol 2022). In the Tagrisso label’s trial descriptions the split between the two is roughly 54-63% exon 19 deletions and 37-45% L858R, depending on the trial.

Exon 20 insertions and other uncommon mutations

Exon 20 insertions are a separate category in the labels: they appear in the amivantamab indications listed below, not in the osimertinib or erlotinib ones. Estimates of how often they occur depend on the denominator and population. The Van Sanden paper reports 0.7% of any-stage NSCLC and 6.1% of EGFR-positive NSCLC in Europe, and also cites regional figures of 4.0% in Asia Pacific, 2.6% in the USA and 2.1% in Latin America. Because those regional numbers come from other sources and are not directly comparable, they are best read as a range. Other uncommon variants, such as exon 18 mutations, are grouped together in the “uncommon” category.

What is T790M?

T790M is different in kind: it is typically a secondary change that emerges after treatment with earlier EGFR TKIs. A 2016 review describes it as the most common mechanism of resistance to first- and second-generation EGFR TKIs but gives no percentage (Wang et al., J Hematol Oncol 2016). A Taiwanese retrospective conference abstract reported T790M in 52.9% of patients after first- or second-generation TKIs, so single-study figures vary (ESMO Asia 2019, abstract 498P). Tagrisso’s label includes a T790M indication after progression on an EGFR TKI. Later resistance patterns are discussed in what comes after Tagrisso.

How are these mutations detected?

In general terms, the mutation is identified by sequencing tumor DNA, or in some settings DNA shed into blood plasma. The Tagrisso label requires that the mutation be “detected by an FDA-approved test,” and lists the acceptable source: tumor tissue for the adjuvant and stage III indications, and plasma or tumor for first-line metastatic use. Pivotal trials used the cobas EGFR Mutation Test (FDA Tagrisso label, section 2.2 and 14). Exactly which test panel is used, and how broad it is, varies by laboratory and is not covered here.

One practical point for readers who track this area: labels tie each approval to a specific mutation group and, usually, to a specific line of therapy, so “EGFR-mutated” on its own is too coarse a category for market sizing or trial comparison. A patient population defined by exon 19 deletions behaves differently, in trial terms, from one defined by exon 20 insertions or by T790M after prior TKI therapy.

Which approved drugs map to which mutation group?

As written in current or recent FDA labels (versions vary; verify against the latest):

• Tagrisso (osimertinib): exon 19 deletions or exon 21 L858R in the adjuvant, unresectable stage III and first-line metastatic settings, and with pemetrexed and platinum chemotherapy first-line; separately, T790M-positive metastatic disease after an EGFR TKI (label revised 09/2024).
• Rybrevant (amivantamab) plus Lazcluze (lazertinib): first-line exon 19 deletions or exon 21 L858R, approved August 19, 2024 based on MARIPOSA (FDA).
• Rybrevant with carboplatin and pemetrexed: exon 19 deletion or L858R disease that progressed on an EGFR TKI (MARIPOSA-2), and first-line for exon 20 insertions (PAPILLON).
• Rybrevant alone: exon 20 insertion disease that progressed on or after platinum chemotherapy (FDA Rybrevant label, revised 08/2025). An FDA-approved subcutaneous form, Rybrevant Faspro, covers the intravenous indications.
• Erlotinib (Tarceva and generics): exon 19 deletions or exon 21 L858R.
• Afatinib (Gilotrif): first-line “non-resistant” EGFR mutations, a broader phrase than the two common mutations; the FDA announced the first generic afatinib tablets on July 14, 2026 (FDA).

Investigational note: in October 2026 ArriVent reported that its phase 3 FURVENT trial of firmonertinib in first-line exon 20 insertion NSCLC did not show a significant PFS benefit over chemotherapy by blinded central review (240 mg arm HR 0.75, p=0.0654) (CancerNetwork). For the competitive picture, see EGFR TKI market landscape, and for how Tagrisso trials are organized by stage, the trial guide.

Next step

For organizations mapping biomarker-defined treatment algorithms, Oncology Resource Group describes its approach at ONCRG Advisory. A broader view is in the osimertinib landscape article.

This article is for informational and competitive-intelligence purposes only and is not medical advice. Approvals, labels and trial results change; verify details against current prescribing information and primary sources.