Choosing a treatment for patients with EGFR mutations

This analysis compared the effectiveness and safety of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors and chemotherapy in patients with mutated EGFR non-small cell lung cancer.

Many non-small cell lung cancer patients present with a mutated (abnormal) EGFR, which can increase the production and spread of cancer cells. For these patients, first-line treatments include EGFR-tyrosine kinase inhibitors, such as erlotinib (Tarceva) and gefitinib (Iressa). These block the activity of EGFR, which slows cancer cell production. Two new EGFR-tyrosine kinase inhibitors, icotinib (BPI-2009H) and afatinib (Gilotrif), have proven effective, but have not been directly compared to each other or to other EGFR-tyrosine kinase inhibitors. 

The current meta-analysis (a comparison of many other studies) compared four EGFR-tyrosine kinase inhibitors currently in use or in development. Twelve trials were included in this analysis, each of which compared erlotinib, gefitinib, icotinib, afatinib, or chemotherapy in a total of 1821 patients with non-small cell lung cancer and EGFR mutations. 1066 of those patients received EGFR-tyrosine kinase inhibitors.

The odds of patients showing an objective response (such as tumor shrinkage) were 5.46 times higher for patients given an EGFR-tyrosine kinase inhibitor than they were when receiving chemotherapy. 66.6% of patients responded to EGFR-tyrosine kinase inhibitors, while 30.9% showed a response to chemotherapy.

The odds of 1-year progression free survival (the time before the cancer begins progressing after treatment) were 7.83 times higher following EGFR-tyrosine kinase inhibitors (42.9% of patients) than following chemotherapy (9.7% of patients). Overall survival times (time until death from any cause) were similar between the groups, with 2-year overall survival following EGFR-tyrosine kinase inhibitors of 49.7% and 51% following chemotherapy.

When comparing between the four EGFR-tyrosine inhibitors, erlotinib was most likely to lead to a high objective response rate (51% higher odds) and 1-year progression free survival rate (38% higher odds). Afatinib was most likely to lead to high 1-year (30% higher odds) and 2-year (27% higher odds) overall survival rates. Erlotinib and afatinib, however, led to more severe side effects, including diarrhea and rash, than did gefitinib and icotinib.

This meta-analysis concluded that EGFR-tyrosine kinase inhibitors were more effective than chemotherapy for patients with an EGFR mutation. However, the four inhibitors evaluated showed different efficacy and safety profiles, as the two that were most effective, erlotinib and afatinib, also led to more severe side effects.