J Thorac Oncol 2019 Apr 16. Epub 2019 Apr 16.
Guangdong Lung Cancer Institute; Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences; Guangzhou; China.
In 2018 research in the field of advanced non-small cell lung cancers (NSCLC) led to an expanded reach and impact of immune-checkpoint inhibitors (ICIs) as part of frontline treatment strategy, regardless of histology subtype, while ICI use was extended to include stage III disease, shifting the prognosis of all these patients. This new standard first-line approach opens a gap in standard second-line treatment, and older combinations may again become standard care after progression on ICIs. The characterization of predictive biomarkers, patient selection, the definition of strategies with ICI combinations upon progression on ICIs, as well as prospective evaluation of the efficacy of ICIs in subpopulations (such as patients with poor performance status or brain metastases) represent upcoming challenges in advanced thoracic malignancies. In oncogenic-addicted NSCLC three major steps were taken during 2018: next-generation tyrosine kinase inhibitors (TKIs) have overtaken more established agents as the new standard of care in EGFR and ALK-positive tumors. Mechanisms of acquired resistance have been reported among patients treated with next-generation EGFR TKIs reflecting the diversity of the landscape. One major step forward was the approval of personalized treatment in very uncommon genomic alterations, mainly fusions. This raises a new question about the challenge of next generation sequencing implementation in daily clinical practice for detecting new and uncommon genomic alterations as well as to capture the heterogeneity of the mechanisms of acquired resistance while on treatment, as well as the need to extend research into new therapeutic strategies to overcome them.