Progress in the Management of Advanced Thoracic Malignancies in 2017

The treatment paradigm of NSCLC underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival both in unselected pretreated patients and in untreated patients with programmed death ligand 1 expression of 50% or more. Furthermore, compelling preliminary results were reported for new combinations of anti–programmed cell death 1/programmed death ligand 1 agents with chemotherapy or anti–cytotoxic T-lymphocyte associated protein 4 inhibitors. The success of the ICIs appeared to extend to patients with SCLC, mesothelioma, or thymic tumors. Furthermore, in SCLC, encouraging activity was reported for an experimental target therapy (rovalpituzumab teserine) and a new chemotherapeutic agent (lurbinectedin). For oncogene-addicted NSCLC, next-generation tyrosine kinase inhibitors (TKIs) (such as osimertinib or alectinib) have demonstrated increased response rates and progression-free survival compared with first-generation TKIs in patients with both EGFR-mutated and ALK receptor tyrosine kinase gene (ALK)-rearranged NSCLC. However, because of the lack of mature overall survival data and considering the high efficacy of these drugs in patients with NSCLC previously exposed to first- or second-generation TKIs, definitive conclusions concerning the best treatment sequence cannot yet be drawn. In addition, new oncogenes such as mutant BRAF, tyrosine-protein kinase met gene (MET) and erb-b2 receptor tyrosine kinase 2 gene (HER2), and ret proto-oncogene (RET) rearrangements have joined the list of potential targetable drivers. In conclusion, the field of thoracic oncology is on the verge of a breakthrough that will open up many promising new therapeutic options for physicians and patients. The characterization of biomarkers predictive of sensitivity or resistance to immunotherapy and the identification of the optimal therapeutic combinations (for ICIs) and treatment sequence (for oncogene-addicted NSCLC) represent the toughest upcoming challenges in the domain of thoracic oncology.