Lung cancer : journal of the International Association for the Study of Lung Cancer
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Differential biology and prognosis between T790M+ and T790M- populations imply immunological differences also. ⋯ T790M+ status was correlated to lower PD-L1 expression. PD-L1 expression might have a prognostic value and interaction with T790M mutation in EGFR-mutant NSCLC.
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TP53 mutations are common in non-small cell lung cancer (NSCLC) and have been reported as prognostic of poor outcome. The impact of TP53 co-mutations in epidermal growth factor receptor (EGFR)-mutated NSCLC is unclear. ⋯ Patients with dual TP53/EGFR mutations, especially missense mutations, had marginally lower response rates and shorter PFS when treated with EGFR TKI therapy. Larger datasets are required to validate these observations.
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Cell-free circulating tumor DNA (ctDNA) next-generation sequencing (NGS) is emerging as a noninvasive technique for detecting targetable mutations. We describe two lung adenocarcinoma cases that show the clinical utility of supplementing tumor biopsy molecular interrogation with ctDNA NGS. For both cases, ctDNA NGS identified actionable mutations that were previously not reported by molecular interrogation of tissue. ⋯ Further tissue analysis demonstrated heterogeneity was the cause of differing results. We demonstrate that supplementing tumor biopsies with ctDNA NGS has a crucial role in patient care. Understanding the causes of differing ctDNA and tumor biopsy genomic results is essential for reconciling findings and application to precision medicine management.
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The first-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, and the second-generation EGFR-TKI, afatinib, have all been approved as standard first-line treatments for advanced EGFR-mutant non-small cell lung cancer (NSCLC) based on superior progression-free survival results compared to platinum doublet chemotherapy regimens. Acquired resistance to an EGFR-TKI inevitably develops after a period of effective drug treatment. ⋯ Osimertinib has become the standard treatment in patients for whom tumor re-biopsy reveals an acquired EGFR T790M mutation following EGFR-TKI therapy. Other third-generation EGFR-TKIs, such as olmutinib, EGF816, and ASP8273, are still in the trial phase.