Lung cancer : journal of the International Association for the Study of Lung Cancer
-
Multicenter Study Clinical Trial
Predictive factors for EGFR-tyrosine kinase inhibitor retreatment in patients with EGFR-mutated non-small-cell lung cancer - A multicenter retrospective SEQUENCE study.
Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations experiencing a response to EGFR-tyrosine kinase inhibitor (TKI) initially. We investigated EGFR-TKI retreatment in patients who had previously received EGFR-TKI followed by chemotherapy. ⋯ EGFR-TKI retreatment was effective in prolonging survival, and was shown to be a worthwhile option for EGFR-mutated NSCLC patients after failure of first-line EGFR-TKI and chemotherapy. The survival benefit was especially pronounced in patients with longer drug holidays from the initial EGFR-TKI and in females with the exon 21 mutation.
-
We evaluated glucose transporter type 1 (GLUT1) and carbonic anhydrase IX (CAIX) expression, together with volume-based18F-fluorodeoxyglucose positron emission tomography (FDG-PET) parameters, in non-small cell lung cancer (NSCLC) patients, and examined the prognostic significance of those parameters according to its histologic subtype. ⋯ MTV and TLG values, and GLUT1 expression, significantly differed between patients with squamous cell carcinoma and adenocarcinoma. High GLUT1 expression levels were significantly associated with MTV and TLG values and adverse clinical outcomes in patients with adenocarcinoma.
-
Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway-targeted immunotherapy has become the standard option of care in the management of lung cancer. The expression of the PD-L1 protein in lung cancer is expected to be a prognostic factor or to predict the response to PD-1-blocking antibodies. However, the association between PD-L1 positivity and the clinicopathological features and patient outcomes in lung squamous cell carcinoma (SCC) remains unclear because the definitive cut-off value for the expression of PD-L1 protein remains to be established. ⋯ The expression of PD-L1 protein was associated with a poor prognosis in lung SCC patients. The 1% cut-off value for PD-L1 might become a better predictive marker than the other cut-off values.
-
A number of small molecule tyrosine kinase inhibitors (TKIs) have now been approved for the treatment of non-small cell lung cancers (NSCLC), including those targeted against epidermal growth factor receptor, anaplastic lymphoma kinase, and ROS1. Despite a wealth of agents developed to target the receptor tyrosine kinase, MET, clinical outcomes have as yet been disappointing, leading to pessimism about the role of MET in the pathogenesis of NSCLC. However, in recent years, there has been a renewed interest in MET exon 14 alterations as potential drivers of lung cancer. ⋯ In this article, we review the current clinical and preclinical data available for these TKIs, along with a number of other potential therapeutic options, including antibodies and immunotherapy. A number of questions remain unanswered regarding the future of MET TKIs, but unfortunately, the development of resistance to targeted therapies is inevitable. Resistance is expected to arise as a result of receptor tyrosine kinase mutation or from upregulation of MET ligand expression; potential strategies to overcome resistance are proposed.
-
Recurrent somatic splice-site alterations at MET exon 14 (METΔ14), which result in exon skipping and MET proto-oncogene, receptor tyrosine kinase (MET) activation, have been characterised. However, their demographic features and clinical outcomes in East Asian lung cancer patients have yet to be determined. ⋯ The OS of METΔ14 mutation positive lung cancer patients is comparable to that of the major driver gene mutation negative lung cancer patients.