Lung cancer : journal of the International Association for the Study of Lung Cancer
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Acquired resistance mutations to anaplastic lymphoma kinase (ALK) inhibitors such as crizotinib and alectinib have been documented in non-small cell lung cancer (NSCLC) patients harboring ALK rearrangement (ALK+). Of note I1171T/N/S mutations in the ALK kinase domain have recently been described by several groups to confer resistance to alectinib, a second-generation ALK inhibitor. Additionally one of these reports demonstrated one ALK+ NSCLC patient harboring an I1171T acquired mutation has responded to ceritinib, another second-generation ALK inhibitor. ⋯ This is the fifth patient case to date demonstrating that ALK I1171 mutation confers resistance to alectinib and the second reported case of ALK I1171 mutation being sensitivity to ceritinib. Substitutions of isoleucine at amino acid 1171 in the ALK kinase domain may distinguish which second generation ALK inhibitor will be effective after crizotinib failure. This case also provides evidence that transaminase elevations is likely a unique adverse event associated with crizotinib and unlikely a "class" effect involving all ALK inhibitors.
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Meta Analysis
Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer.
Three epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) - afatinib, erlotinib, and gefitinib - are available for the treatment of patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). Given the long-term exposure of such patients to EGFR-TKIs, the toxicological properties of these agents in these individuals may differ from those observed in unselected patients. We compared the frequencies of severe adverse events (AEs) among EGFR mutation-positive NSCLC patients treated with these three EGFR-TKIs. ⋯ Such information on AEs should facilitate selection of the most appropriate EGFR-TKI for EGFR mutation-positive NSCLC patients with regard to mitigation of the risk for certain types of toxicity.
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Programmed cell death-1 (PD-1)/programmed cell death-ligand-1 (PD-L1) pathway-targeted immunotherapy has beneficial therapeutic effects in pulmonary squamous cell carcinoma (SqCC) patients. However, the expression patterns of PD-1 and PD-1 ligands (PD-Ls) in pulmonary SqCC remain unclear. Moreover, the association between the PD-1/PD-Ls pathway and the status of oncogenic drivers in pulmonary SqCC is unknown. ⋯ PD-L1 and PD-L2 expression in pulmonary SqCC is associated with an increased number of CD8(+) TILs and increased MET expression, which might provide therapeutic insight into targeting the PD-1/PD-Ls pathway in pulmonary SqCC.
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We describe a case of dysgeusia that developed gradually over one week after initiation of crizotinib administration for treatment of ALK-positive non-small cell lung cancer, necessitating discontinuation of the agent. The symptom was accompanied by progressive loss in appetite and body weight. ⋯ The present case indicates that dysgeusia is an important toxicity associated with crizotinib, which could adversely affect nutritional condition and quality of life. We describe the clinical course and present a review of crizotinib-induced dysgeusia.
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Comparative Study
Comparison of clinical outcome of stage I non-small cell lung cancer treated surgically or with stereotactic radiotherapy: results from propensity score analysis.
Guideline-specified curative therapies for a clinical stage I non-small cell lung cancer (NSCLC) are either lobectomy or Stereotactic Ablative Radiotherapy (SABR). As outcomes of prospective randomized clinical trials comparing these modalities are unavailable, we performed a propensity-score matched analysis to create two similar groups in order to compare clinical outcomes. ⋯ In this study we found no significant differences in overall survival in propensity matched patients diagnosed with stage I NSCLC treated either surgically or with SABR. After 3 years there seems to be a trend toward improved survival in patients who were treated surgically.