ReviewUncommon EGFR mutations in advanced non-small cell lung cancer

- Uncommon or 'non-classical' EGFR mutations, including complex mutations are increasingly reported.
- Exon 20 insertions have a poor response to EGFR-TKIs.
- Mutations in L861Q, S768I and G718X have an inferior response to EGFR-TKIs.
- Complex mutations harboring an uncommon mutation have a better response than single mutations.

Molecular profiling in advanced non-small cell lung cancer (NSCLC) has allowed for the detection of actionable mutations, which has revolutionized the treatment paradigm in this highly fatal disease. Mutations involving the epidermal growth factor receptor (EGFR) gene are most common and the 'classical mutations', exon 19 deletions and the point mutation L858R at exon 21, predict response to EGFR tyrosine kinase inhibitors (TKIs). The 'uncommon' EGFR mutations account for 10-18% of all EGFR mutations and primarily consist of exon 20 insertions, exon 18 point mutations and complex mutations. Improved detection techniques have broadened the spectrum of reported aberrations within the 'uncommon group' but response to TKIs is variable and not fully elucidated. This review provides an overview of the biology and incidence of uncommon EGFR mutations and summarizes reported outcomes when treated with EGFR-TKIs.