Targeted therapies for unresectable stage III non-small cell lung cancer

Until recently, the standard treatment in unresectable stage III non-small cell lung cancer was concurrent chemoradiotherapy, but often with dismal outcome. The introduction of consolidation treatment with immune checkpoint inhibitors has shifted the treatment landscape and prognosis of these patients. However, patients whose tumors harbors an epidermal growth factor receptor (EGFR) mutation derived less benefit, with an increased risk of immune-related adverse events. Moreover, current data suggested that patients with oncogenic addicted tumors, mainly EGFR-positive tumors, and also anaplastic lymphoma kinase (ALK)-positive have poorer progression free survival after chemoradiotherapy. Indeed, these tumors have also inferior distant control compared with those who have wild-type disease, especially in the central nervous system, highlighting the need for assessing the role of targeted therapies in this patient population. It is speculated that outcome could probably increase with a consolidation treatment strategy including an EGFR tyrosine kinase inhibitor. However, a personalized treatment approach is not considered standard of care in this setting due to lack of robust evidence, as the majority of trials were performed in unselected patients, number of patients is limited and the majority of these studies were underpowered. In this review we summarize the role of tyrosine kinase inhibitors in unresectable stage III NSCLC, specifically focusing on EGFR-mutant tumors.