Abstract
The principal of preferentially selecting patients most likely to benefit from therapy according to their genetic profile has led to substantial clinical benefit in some tumour types, and has potential to considerably refine treatment in advanced non-small cell lung cancer (NSCLC). Effective, reliable use of molecular biomarkers to inform clinical practice requires the standardization of testing methods and careful assessment of biomarkers' predictive and prognostic value. Although a number of studies show that patients with activating mutations in exons 18–21 respond particularly well to gefitinib and erlotinib, a prospective, randomized study was needed to differentiate between the prognostic and predictive value of epidermal growth factor receptor (EGFR) mutations. From one such study, it appears that mutational testing should become standard at diagnosis, at least for adenocarcinoma patients with a never or low smoking history, as clinical predictors are insufficient to optimize treatment. However, outstanding questions remain: what are the treatment options for patients with tumours resistant to erlotinib/gefitinib? What conclusions about treatment can we draw from EGFR copy number or KRAS mutation status? What role should anti-EGFR antibodies play in NSCLC treatment, and in which patients? This review considers current evidence linking biomarker profile to efficacy of EGFR-targeted therapy in NSCLC, and clinical implications of recent findings.
- Biomarker
- epidermal growth factor receptor
- epidermal growth factor receptor inhibitors
- genetic profiling
- mutational testing
- non-small cell lung cancer
- ERS