Targeted Therapy in Advanced and Metastatic Non-Small Cell Lung Cancer. An Update on Treatment of the Most Important Actionable Oncogenic Driver Alterations

SIMPLE SUMMARY: The treatment of advanced and metastatic non-small cell lung cancer (NSCLC) has changed dramatically in recent years due to advanced molecular diagnostics and the recognition of targetable oncogenic driver alterations. This has led to the development of very effective new targeted agents, and thus to a relevant progress in the treatment of oncogene-addicted NSCLC. While the treatment of EGFR-mutated and ALK-rearranged NSCLC is well-established, new targeted therapy options have emerged for other oncogenic alterations. In this comprehensive review article, we discuss the major molecular alterations in NSCLC and the corresponding therapeutic options. ABSTRACT: Due to groundbreaking developments and continuous progress, the treatment of advanced and metastatic non-small cell lung cancer (NSCLC) has become an exciting, but increasingly challenging task. This applies, in particular, to the subgroup of NSCLC with oncogenic driver alterations. While the treatment of epidermal growth factor receptor (EGFR)-mutated and anaplastic lymphoma kinase (ALK)-rearranged NSCLC with various tyrosine kinase inhibitors (TKIs) is well-established, new targets have been identified in the last few years and new TKIs introduced in clinical practice. Even for KRAS mutations, considered for a long time as an “un-targetable” alteration, promising new drugs are emerging. The detection and in-depth molecular analysis of resistance mechanisms has further fueled the development of new therapeutic strategies. The objective of this review is to give a comprehensive overview on the current landscape of targetable oncogenic alterations in NSCLC.