EGFR Inhibitors in the treatment of non–small cell lung cancer patients

This meta-analysis (an analysis of data combined from several similar trials) examined the impact of EGFR tyrosine kinase inhibitors (TKI's) on progression-free survival (PFS) and the overall survival (OS) of advanced non small-cell lung cancer (NSCLC) patients.

Non-small-cell lung cancer (NSCLC) cells may contain genetic mutations that cause cells to grow and spread rapidly, promoting tumor formation. A mutation in the epidermal growth factor receptor (EGFR) gene is responsible for one form of NSCLC. Patients with EGFR-mutation positive NSCLC respond to treatment with a class of drugs known as tyrosine kinase inhibitors (TKIs). TKIs, such as erlotinib (Tarceva), gefitinib (Iressa) or afatinib (Gilotrif), block the stimulating action of EGFR on cellular growth.

TKI's have been shown to improve progression free survival (PFS; the amount of time between treatment and until the disease worsens or progresses) in several small trials. However, no large analysis to date has reproduced this finding, and no study has managed to show a similar benefit on overall survival.

23 trials with a total of 14,570 patients were included in this analysis. 4473 (31%) of these patients were found positive for EGFR mutations (EGFR-positive NSCLC). The effect of TKI's on PFS and OS was assessed in both EGFR-positive and EGFR-negative NSCLC patients.

When TKI therapy was given as first-line therapy (first choice of treatment), the risk of disease progression was reduced by 57% for EGFR-positive NSCLC patients. When TKI's were given as second-line therapy (after first-line therapy has failed and the disease has progressed) the risk of disease progression was reduced by 66% for EGFR-positive NSCLC patients. For EGFR-negative NSCLC patients no benefit was seen on PFS regardless of treatment timing.

4 trials compared chemotherapy to TKI therapy (alone or combined with chemotherapy). When combined chemotherapy-TKI therapy was received, the risk of disease progression was reduced by 46% for EGFR-positive NSCLC patients, and also by 18% for EGFR-negative NSCLC patients. In EGFR positive patients, the combined treatment was not found to be more effective than treatment with TKIs alone.

Unfortunately, TKI treatment showed no benefit on overall survival for both EGFR-positive and EGFR-negative NSCLC patients.

EGFR-TKIs therapy significantly delays disease progression in EGFR-positive NSCLC patients. However, no impact on overall survival was demonstrated. This meta-analysis concluded that TKIs should be considered as first-line therapy for EGFR-positive NSCLC patients.

This analysis did not determine if the different TKIs (gefitinib, erlotinib, or afatinib) were equally effective in treating lung cancer.

Consult with your physician regarding the benefits of tyrosine kinase inhibitors (TKIs) in the treatment of non-small cell lung cancer.