Epidermal growth factor receptor (EGFR) mt+ nonsmall cell lung cancer (NSCLC) were the first molecularly described NSCLC with an established ‘targeted’ therapy inhibiting mutated EGFR [EGFR tyrosine kinase inhibitor (TKI)]. EGFR TKI of first and second generation have led to an unprecedented improvement in objective response rate, progression-free survival (PFS) and overall survival (OS) compared with chemotherapy with a significantly reduced toxicity and improved quality of life. Fast elucidation of the most frequent resistance mechanism against first and second-generation TKI, T790M, led to the approval of the third-generation TKI osimertinib in second line.
Recently, the FLAURA study showed an impressive PFS benefit and immature OS data for osimertinib against solely first-generation TKI's. Also, the ARCHER study comparing dacomitinib against first-generation TKI showed a PFS and also OS benefit. Two studies combining EGFR TKI and antiangiogenesis showed PFS but no OS benefit. Lately, the combination of TKI and chemotherapy has seen a revival with the NEJ009 study, resulting in an impressive median OS of 55 months.
Therefore, potentially four different therapeutic options are available in first-line therapy of EGFR mt+ NSCLC, first, second, third generation, TKI + antiangiogenic agent and TKI + chemotherapy. The purpose of the review is to help to guide physicians to decide in their treatment choice and discuss potential directions of research.
Department of Hematology and Oncology, University Dept Internal Medicine-Oncology, Pius-Hospital, Medical Campus University of Oldenburg, Oldenburg, Germany
Correspondence to Frank Griesinger, Department of Hematology and Oncology, University Dept Internal Medicine-Oncology, Pius-Hospital, Medical Campus University of Oldenburg, Georgstrasse 12, D-26121 Oldenburg, Germany. Tel: +49 441 229 1610; fax: +49 441 229 1607; e-mail: firstname.lastname@example.org,email@example.com