Personalized medicine in non-small-cell lung cancer: has it come of age?

摘要

In his editorial on the landmark study of Schiller et al. in the New England Journal of Medicine, Carney stated that chemotherapy in advanced lung cancer had reached a plateau and that the use of specific biologic targets would offer optimism and hope that mortality from this disease may be reduced [l]. Approximately 10 years later the landscape of non-small-cell lung cancer (NSCLC) has changed significantly and his optimism was confirmed. Even though chemotherapy still remains the backbone for most of our patients, a substantial number of patients receive small molecules with a different mode of action offering them much greater and longer benefit compared with chemotherapy. The identification of mutations in the EGFR in 2004 and the proof that these mutations are associated with an increased sensitivity of the tumor to EGFR tyrosine kinase inhibitors (TKIs) [2] became the first, and so far greatest, step towards personalized therapy in NSCLC. It took some years to prove the first case reports in randomized prospective trials, but today there is no doubt that the presence of an activating EGFR mutation is a strong prognostic and predictive marker in NSCLC. The biology of the mutated tumor is so different from common NSCLC that it should be considered to regard this disease as a new entity of lung cancer. The results of a variety of clinical trials that showed a highly increased efficacy of EGFR-TKI compared with conventional chemotherapy in patients harboring activating EGFR mutations led to routine testing for EGFR mutations in patients with advanced NSCLC. The question of which patients are to be screened and when they should be screened is still under discussion and will show differences in various regions. However, there is a consensus that, in general, screening for EGFR mutations should be offered to patients with non-squamous cell NSCLC.