Targeted Therapies for Lung Cancer Patients With Oncogenic Driver Molecular Alterations

Lung cancer has traditionally been classified by histology. However, a greater understanding of disease biology and the identification of oncogenic driver alterations has dramatically altered the therapeutic landscape. Consequently, the new classification paradigm of non-small-cell lung cancer is further characterized by molecularly defined subsets actionable with targeted therapies and the treatment landscape is becoming increasingly complex. This review encompasses the current standards of care for targeted therapies in lung cancer with driver molecular alterations. Targeted therapies for exon 19 deletion and L858R mutations, and and rearrangements are well established. However, there is an expanding list of approved targeted therapies including for V600E, exon 20 insertion, and G12C mutations, exon 14 alterations, and and rearrangements. In addition, there are numerous other oncogenic drivers, such as exon 20 insertion mutations, for which there are emerging efficacy data for targeted therapies. The importance of diagnostic molecular testing, intracranial efficacy of novel therapies, the optimal sequencing of therapies, role for targeted therapies in early-stage disease, and future directions for precision oncology approaches to understand tumor evolution and therapeutic resistance are also discussed.