Resistance to osimertinib in advanced EGFR-mutated NSCLC: a prospective study of molecular genotyping on tissue and liquid biopsies

Leonetti, A.; Verzè, M.; Minari, R.; Perrone, F.; Gnetti, L.; Bordi, P.; Pluchino, M.; Nizzoli, R.; Azzoni, C.; Bottarelli, L.; Lagrasta, C. A. M.; Mazzaschi, G.; Buti, S.; Gasparro, D.; Cosenza, A.; Ferri, L.; Majori, M.; De Filippo, M.; Ampollini, L.; La Monica, S.; Alfieri, R.; Silini, E. M.; Tiseo, M.

doi:10.1038/s41416-023-02475-9

Cited by 15 publications

(2 citation statements)

References 32 publications

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“…Therefore, it offers a convenient, fast and precise approach to identify targetable oncogene mutations and resistance mechanisms in addition to, and sometimes instead of, the traditional methods. [27][28][29][30] Although initially primarily used for the detection of EGFR T790M NM_005228.5(EGFR):c.2369C>T mutations linked to acquired resistance to therapy in NSCLC, the application has been expanded to the early identification of other emerging resistance mutations, such as EGFR C797S NM_005228.5(EG-FR):c.2390G>C. [31][32][33][34] This highlights the importance of tracking mutations throughout the disease course, as it is essential to timely clinical decision-making and treatment planning. 25 35 While there are advantages to NGS with liquid biopsy, there have been issues with the determination of the status of fusions when using cell-free DNA (cfDNA)-based methods.…”

Section: How This Study Might Affect Research Practice or Policymentioning

confidence: 99%

Implementation of an ISO 15189 accredited next generation sequencing service for cell-free total nucleic acid (cfTNA) analysis to facilitate driver mutation reporting in blood: the experience of a clinical diagnostic laboratory

Werner,

Crosbie,

Dorney

et al. 2024

J Clin Pathol

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AimsNext generation sequencing (NGS) on tumour tissue is integral to the delivery of personalised medicine and targeted therapy. NGS on liquid biopsy, a much less invasive technology, is an emerging clinical tool that has rapidly expanded clinical utility. Gene mutations in cell-free total nucleic acids (cfTNA) circulating in the blood are representative of whole tumour biology and can reveal different mutations from different tumour sites, thus addressing tumour heterogeneity challenges.MethodsThe novel Ion Torrent Genexus NGS system with automated sample preparation, onboard library preparation, templating, sequencing, data analysis and Oncomine Reporter software was used. cfTNA extracted from plasma was verified with the targeted pan-cancer (~50 genes) Oncomine Precision Assay (OPA). Assessment criteria included analytical sensitivity, specificity, limits of detection (LOD), accuracy, repeatability, reproducibility and the establishment of performance metrics.ResultsAn ISO 15189 accredited, minimally invasive cfTNA NGS diagnostic service has been implemented. High sensitivity (>83%) and specificity between plasma and tissue were observed. A sequencing LOD of 1.2% was achieved when the depth of coverage was >22 000×. A reduction (>68%) in turnaround time (TAT) of liquid biopsy results was achieved: 5 days TAT for in-house analysis from sample receipt to a final report issued to oncologists as compared with >15 days from reference laboratories.ConclusionTumour-derived somatic variants can now be reliably assessed from plasma to provide minimally invasive tumour profiling. Successful implementation of this accredited service resulted in:Appropriate molecular profiling of patients where tumour tissue is unavailable or inaccessible.Rapid TAT of plasma NGS results.

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Section: How This Study Might Affect Research Practice or Policymentioning

confidence: 99%

Implementation of an ISO 15189 accredited next generation sequencing service for cell-free total nucleic acid (cfTNA) analysis to facilitate driver mutation reporting in blood: the experience of a clinical diagnostic laboratory

Werner,

Crosbie,

Dorney

et al. 2024

J Clin Pathol

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“… 5 , 6 Bypass pathway activation, such as mesenchymal–epithelial transition factor (MET) amplification, 7 Erb‐b2 receptor tyrosine kinase 2 (ERBB2) amplification, 8 V‐Raf murine sarcoma viral oncogene homolog B (BRAF) mutations, 9 Kirsten rat sarcoma virus (KRAS) mutations, 10 and oncogenic fusions 11 , 12 are also important mechanisms of resistance. 13 , 14 In addition to EGFR inhibition, there is clinical evidence that inhibiting MET amplification, 15 , 16 , 17 ERBB2 amplification, 18 BRAF mutation, 19 rearranged during transfection (RET) fusion, 11 , 20 and anaplastic lymphoma kinase (ALK) fusion 12 may be effective in controlling EGFR‐TKI‐resistant lung cancers. Next‐generation sequencing (NGS) is a powerful tool to detect dozens or hundreds of possible oncogenic drivers at a time.…”

Section: Introductionmentioning

confidence: 99%

Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first‐line EGFR inhibitor resistance in lung cancer

Lin,

Ho,

Hsu

et al. 2023

Cancer Medicine

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IntroductionAccording to current International Association for the Study of Lung Cancer guideline, physicians may first use plasma cell‐free DNA (cfDNA) methods to identify epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)‐resistant mechanisms (liquid rebiopsy) for lung cancer. Tissue rebiopsy is recommended if the plasma result is negative. However, this approach has not been evaluated prospectively using next‐generation sequencing (NGS).MethodsWe prospectively enrolled patients with lung cancer with first‐line EGFR‐TKI resistance who underwent tissue rebiopsy. The rebiopsied tissues and cfDNA were sequenced using targeted NGS, ACTDrug®+, and ACTMonitor®Lung simultaneously. The clinicopathological characteristics and treatment outcomes were analyzed.ResultsTotally, 86 patients were enrolled. Twenty‐six (30%) underwent tissue biopsy but the specimens were inadequate for NGS. Among the 60 patients with paired tissue and liquid rebiopsies, two‐thirds (40/60) may still be targetable. T790M mutations were found in 29, including 14 (48%) only from tissue and 5 (17%) only from cfDNA. Twenty‐four of them were treated with osimertinib, and progression‐free survival was longer in patients without detectable T790M in cfDNA than in patients with detectable T790M in cfDNA (p = 0.02). For the 31 T790M‐negative patients, there were six with mesenchymal–epithelial transition factor (MET) amplifications, four with ERBB2 amplifications, and one with CCDC6‐RET fusion. One with MET amplification and one with ERBB2 amplification responded to subsequent MET and ERBB2 targeting agents respectively.ConclusionsNGS after EGFR‐TKI resistance may detect targetable drivers besides T790M. To do either liquid or tissue NGS only could miss patients with T790M. To do tissue and liquid NGS in parallel after EGFR‐TKI resistance may find more patients with targetable cancers.

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Graph-Based Spatial Proximity of Super-Resolved Protein–Protein Interactions Predicts Cancer Drug Responses in Single Cells

Zhang,

Cai,

Wang

et al. 2024

Cel. Mol. Bioeng.

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Resistance to osimertinib in advanced EGFR-mutated NSCLC: a prospective study of molecular genotyping on tissue and liquid biopsies

Cited by 15 publications

References 32 publications

Implementation of an ISO 15189 accredited next generation sequencing service for cell-free total nucleic acid (cfTNA) analysis to facilitate driver mutation reporting in blood: the experience of a clinical diagnostic laboratory

Implementation of an ISO 15189 accredited next generation sequencing service for cell-free total nucleic acid (cfTNA) analysis to facilitate driver mutation reporting in blood: the experience of a clinical diagnostic laboratory

Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first‐line EGFR inhibitor resistance in lung cancer

Graph-Based Spatial Proximity of Super-Resolved Protein–Protein Interactions Predicts Cancer Drug Responses in Single Cells

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