When should we order a next generation sequencing test in a patient with cancer?

Colomer, Ramón; Mondéjar, Rebeca; Romero-Laorden, Nuria; Alfranca, Arántzazu; Sánchez‐Madrid, Francisco; Quintela‐Fandino, Miguel

doi:10.1016/j.eclinm.2020.100487

Cited by 126 publications

(101 citation statements)

References 59 publications

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“…At this moment, several guidelines favor NGS rather than multiple single-gene tests as the preferred test to identify actionable oncogenic drivers. 66 It is becoming clear that selecting the adequate NGS-based assay is important because each technique has its own caveats. DNA-based large-gene-panel NGS assay is probably the most widely available test for broad molecular sequencing of cancer patients.…”

Section: Resultsmentioning

confidence: 99%

Genomic profiling in non-small-cell lung cancer in young patients. A systematic review

et al. 2021

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Lung cancer in young patients is an uncommon and understudied entity that harbors distinctive epidemiological, clinic-demographic, and genomic features. We carried out a systematic review of genomic profiling in young patients with lung cancer from 2010 to 2020 in the main electronic databases and selected 23 manuscripts. Lung cancer in young patients occurs more frequently in women with adenocarcinoma histology and at more advanced stages. Some studies report higher oncogenic genomic alteration in this population, with higher anaplastic lymphoma kinase rearrangements, a distinct profile of epidermal growth factor receptor mutations, and other novel genomic alterations. Although still uncommon, the implementation of next-generation sequencing (NGS) has shed some light on germline genomic alterations associated with lung cancer in young patients. Although outcomes when compared with the older population are conflicting, the overall prognosis is still poor in this subset of patients and efforts to find targetable genomic alterations should be made to improve survival.

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Section: Resultsmentioning

confidence: 99%

Genomic profiling in non-small-cell lung cancer in young patients. A systematic review

et al. 2021

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“…There are several approaches available to test for these known alterations, including Sanger sequencing, quantitative reverse transcription PCR (qRT-PCR) and DNA/RNA-based next generation sequencing (NGS) [29]. Sanger can sequence a low number of genes (1-20 targets) [30] and qRT-PCR can only test one at a time, while NGS allows for detection of multiple gene alterations from a single sample, providing a higher throughput than traditional methods [31,32]. Given the complexity and diversity of the mutations driving METex14, NGS represents the most suitable method of testing.…”

Section: Metex14 In Non-small Cell Lung Cancermentioning

confidence: 99%

Capmatinib for patients with non-small cell lung cancer with MET exon 14 skipping mutations: A review of preclinical and clinical studies

Smit

Bauer

2021

Cancer Treatment Reviews

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The mesenchymal-epithelial transition (MET) receptor tyrosine kinase binds the hepatocyte growth factor to activate downstream cell signaling pathways involved in cell proliferation, survival, and migration. Several genetic mechanisms can result in an aberrant activation of this receptor in cancer cells. One such activating mechanism involves the acquisition of gene mutations that cause MET exon 14 skipping (METex14) during mRNA splicing. Mutations leading to METex14 are found in approximately 3-4% of patients with non-small cell lung cancer (NSCLC). Accumulating evidence suggests that METex14 is a true, independent oncogenic driver in NSCLC, as well as being an independent prognostic factor for poorer survival in patients with NSCLC. The successes of target therapies have relied on improved understanding of the genetic alterations that lead to the dysregulation of the molecular pathways and more advanced molecular diagnostics. Multiple efforts have been made to target the MET pathway in cancer; however, real clinical progress has only occurred since the emergence of METex14 as a valid biomarker for MET inhibition. Capmatinib is a highly potent and selective type Ib inhibitor of MET. Following preclinical demonstration of activity against MET-dependent cancer cell line growth and METdriven tumor growth in xenograft models, data from a phase 1 clinical trial showed an acceptable safety profile of capmatinib and preliminary evidence of efficacy in patients with MET-dysregulated NSCLC. The multicohort GEOMETRY mono-1 phase 2 trial reported objective response rates of 68% and 41% in treatment-naïve and in pre-treated patients with METex14 advanced NSCLC, respectively. These results have supported the approval of capmatinib by the US Food and Drug Administration for patients with metastatic NSCLC harboring METex14.

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“…Gene panel testing to detect actionable genomic alterations for therapeutic purpose could test a number of cancer associated genes in a single round by advance in NGS technology, which might replace existing clinical management, including molecular testing of single gene (e.g., BRAF, ALK) or composite genetic signature (e.g., mismatch repair), in the view of cost effectiveness and time-consuming [21]. On the other hand, the NGS test was not basically indicated for cancers at early stage [22]. In this study, we performed practical clinical sequencing for patients with refractory solid tumor using four types of gene panel testing by NGS.…”

Section: Discussionmentioning

confidence: 99%

Clinical benefit for clinical sequencing using cancer panel testing

et al. 2021

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Background Clinical sequencing using a panel of genes has recently been applied worldwide for patients with refractory solid tumors, but the significance of clinical sequencing using gene panel testing remains uncertain. Here we sought to clarify the feasibility and utility of clinical sequencing in the treatment of refractory tumors at our hospital. Methods A total of 39 patients with advanced solid tumors treated at our hospital between 2018 and 2020 were enrolled in the clinical sequencing. Among them, we identified 36 patients whose tissue samples were of suitable quality for clinical sequencing, and we analyzed the genomic profiles of these tumors. Results Pathogenic alterations were detected in 28 (78%) of the 36 patients. The most common mutation was TP53 (55%), followed by KRAS (22%), and the highest frequency of gene amplification was ERBB2 (17%). Nine of the 36 patients were identified as candidates for novel molecular-targeted therapy based on their actionable gene alterations, but only one case ended up receiving novel targeted therapy following the genetic tests. Conclusions Our current results suggested that clinical sequencing might be useful for the detection of pathogenic alterations and the management of additional cancer treatment. However, molecular target based on actionable genomic alteration does not always bridge to subsequent therapy due to clinical deterioration, refusal for unapproved drug, and complexity of clinical trial access. Both improved optimal timing of clinical sequencing and a consensus about its off-label use might help patients receive greater benefit from clinical sequencing.

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When should we order a next generation sequencing test in a patient with cancer?

Cited by 126 publications

References 59 publications

Genomic profiling in non-small-cell lung cancer in young patients. A systematic review

Genomic profiling in non-small-cell lung cancer in young patients. A systematic review

Capmatinib for patients with non-small cell lung cancer with MET exon 14 skipping mutations: A review of preclinical and clinical studies

Clinical benefit for clinical sequencing using cancer panel testing

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