Abstract
The principle 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 nonsmall cell lung cancer (NSCLC). Effective, reliable use of molecular biomarkers to inform clinical practice requires the standardisation of testing methods and careful assessment of biomarkers’ predictive and prognostic value.
Although a number of studies have shown that patients with activating mutations in exons 18–21 of the epidermal growth factor receptor (EGFR) gene respond particularly well to gefitinib and erlotinib, a prospective, randomised study was needed to differentiate between the prognostic and predictive value of EGFR mutations. From one such study, it appeared 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 optimise 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
- nonsmall cell lung cancer
Footnotes
Support Statement
Boehringer Ingelheim provided financial support for the assistance of Ogilvy Healthworld Medical Education.
Statement of Interest
Statements of interest for all authors can be found at www.erj.ersjournals.com/site/misc/statements.xhtml
- Received November 11, 2009.
- Accepted May 6, 2010.
- ©ERS 2011