A Subset of EGFR Mutations in Lung Cancer Is Associated with Resistance to TKI Treatment

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.

TKIs Are Effective First-Line Treatment in EGFR-Mutant Advanced NSCLC

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.

Research paper: http://link.springer.com/article/10.1007/s11523-013-0258-9/fulltext.html