title: Second-Line Treatment of NSCLC-The Pan-ErbB Inhibitor Afatinib in Times of Shifting Paradigms.
abstract: In contrast to the established role of epidermal growth factor receptor (EGFR) inhibitors for the first-line treatment of patients with non-small cell lung cancer (NSCLC) harboring activatingEGFRmutations, the role of EGFR blockade and ofEGFRmolecular testing in the second-line treatment remains less clear. The irreversible pan-ErbB family inhibitor afatinib (Gi(l)otrif®) was recently FDA- and EMA-approved for the second-line treatment of NSCLC with squamous cell histology irrespective of theEGFRmutational status (LUX-Lung 8). Contrariwise, results from the TAILOR and DELTA trials among retrospective biomarker analyses show the predictive value of theEGFRmutational status for efficacy of reversible EGFR inhibitors also as a second-line therapy. This mini review critically summarizes the current role of EGFR-targeting strategies in the second-line treatment of NSCLC with special respect to afatinib in light of emergingT790M-specific EGFR and immune check point inhibitors. The review also emphasizes the urgent need for reliable biomarkers to guide therapeutic decision-making and outlines prospective changes to the second-line landscape with some of the current second-line treatment concepts likely to be moved to the first-line.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; West German Cancer Center Essen, Department of Medical Oncology, Division of Thoracic Oncology, University Hospital Essen, Essen, North-Rhine Westphalia, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Köhler
keywords: EGFR mutation; NSCLC; T790M-specific inhibitors; TKI; afatinib; checkpoint blockade; second-line treatment; squamous cell carcinoma