Non-small cell lung cancers (NSCLC) with a mutation in the EGFR gene can usually be treated with EGFR-tyrosine kinase inhibitors (TKIs) such as erlotinib (Tarceva), gefitinib (Iressa), afatinib, neratinib, or dacomitinib. However, mutations that are located in a region of the EGFR gene called exon 20 are associated with a lack of response to TKI treatment. A study of tumor tissue from adenocarcinoma (a type of NSCLC) found that such exon 20 mutations are present in approximately 10% of EGFR-mutant adenocarcinoma and 3% of all adenocarcinoma, that they are more common in NSCLC patients who never smoked, and that there are a wide variety of different exon 20 mutations, some of which may be more responsive to TKI treatment than others.
Four phase III studies compared the tyrosine kinase inhibitors (TKIs) erlotinib (Tarceva) or gefitinib (Iressa) to standard chemotherapy as first-line treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). TKI treatment increased progression-free survival (ie, the length of time without the cancer worsening), but did not improve overall survival compared to chemotherapy. In one study, TKI-treated patients maintained a higher quality of life for longer than chemotherapy-treated patients. The findings suggest that TKI treatment should become the standard first-line treatment in advanced NSCLC with mutations in the EGFR gene.