Physics

Internal medicine

Receptor

Erlotinib

Epidermal growth factor receptor

Incidence (geometry)

Biology

Gene

Optics

Cancer

Oncology

T790M

Lung cancer

Osimertinib

Mutation

Gefitinib

Afatinib

Tyrosine kinase

Cancer research

Genetics

Medicine

Current Oncology

Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted a systematic review to investigate the available data on this patients’ subgroup. Overall, we found a high heterogeneity in the incidence of compound mutations (4–26% of total EGFR mutant cases), which is dependent on the different testing methods adopted and the specific mutations considered. In addition, the relative incidence of distinct compound subclasses identified is reported with extreme variability in different studies. Preclinical and clinical data, excluding de novoEGFR exon 20 p.T790M compound mutations, show good responses with EGFR tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% with either first- or second-generation TKIs; combined common plus uncommon: RR 40–80% and 100% with first-generation TKIs and afatinib, respectively; combined uncommon: RR 20–70%, ~80% and ~75% with first-generation TKIs, afatinib and osimertinib, respectively). Overall, data are consistent in supporting the use of EGFR TKIs in treating compound EGFR mutations, taking into account different sensitivity profile of accompanying EGFR mutations for selecting the most adequate EGFR TKI for individual patients.

Uncommon EGFR Compound Mutations in Non-Small Cell Lung Cancer (NSCLC): A Systematic Review of Available Evidence