Journal of Thoracic Oncology 2018 January 10 [Epub ahead of print] [Link]

Ferrara R, Mezquita L, Besse B


The treatment paradigm of non-small cell lung cancer (NSCLC) underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival (OS) both in unselected pretreated patients and in untreated patients with PD-L1 expression ≥50%. Furthermore, compelling preliminary results were reported for new combinations of anti-PD-1/PD-L1 agents with chemotherapy or anti-CTLA4 inhibitors. The success of the ICIs appeared to extend to patients with small cell lung cancer (SCLC), mesothelioma or thymic tumors. Furthermore, in SCLC, encouraging activity was reported for an experimental target therapy (Rova T) and a new chemotherapeutic agent (lurbinectedin). For oncogene-addicted NSCLC, next-generation tyrosine kinase inhibitors (such as osimertinib or alectinib) have demonstrated increased response rates and progression-free survival compared to first-generation TKIs in both EGFR-mutated and ALK-rearranged NSCLC patients. However, due to the lack of mature OS data and considering the high efficacy of these drugs in NSCLC patients previously exposed to first or second-generation TKIs, definitive conclusions cannot yet be drawn concerning the best treatment sequence. In addition, new oncogenes such as mutant BRAF, MET and HER2, and RET rearrangements have joined the list of potential targetable drivers. In conclusion, the field of thoracic oncology is on the verge of a breakthrough which will open up many promising new therapeutic options for physicians and patients. The characterization of predictive biomarkers 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.