Treatment of EGFR-mutant non-small-cell lung cancer in advanced stages

Non-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer and about 15% of these tumours harbour an underlying EGFR-mutation. This is a large patient population that can benefit from targeted EGFR tyrosine kinase inhibitors (TKI) such as gefitinib, erlotinib and afatinib, especially in advanced stages of disease. EGFR-TKI-therapy results in a better response rate, progression-free survival and quality of life compared to standard platinum-based chemotherapy. In patients with advanced stage-EGFR mutant NSCLC, EGFR-TKI's are now widely accepted as first line treatment. Side-effects of EGFR-TKI therapy include diarrhoea and skin rash, occuring in more than 50% of the cases. Eventually, resistance against the EGFR-TKI develops and this still limits survival. Several therapeutic options are being investigated, with current focus on combination therapy of multiple pathways and development of third-generation EGFR-TKI's. This third generation includes molecules with a larger therapeutic window which allows treatment of T790M-resistance. Repeated tumour sequencing using "liquid biopsies" allows identification and treatment of the underlying mechanism of resistance. In this article, a case of NSCLC with a typical profile for EGFR-mutation is presented. Targeted TKI treatment, its side-effects and mechanisms of resistance are discussed.

Jaar van publicatie:2017