Successful Treatment and Retreatment With Erdafitinib for a Patient With FGFR3-TACC3 Fusion Squamous NSCLC: A Case Report

Pham, Chi Hoa; Lang, Daenielle; Iams, Wade T.

doi:10.1016/j.jtocrr.2023.100511

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…In case 1, the MI Tumor Seek Hybrid TM test confirmed the OFA sNGS detected EGFR p.E746_A750del and MET p.G843R variants and identified two additional VUSs. Notably, all sNGS negative cases harbored mutant gene variants with prognostic significance at the WES level but only one specimen (case 4) harbored a potentially actionable FGFR3::TACC3 fusion that defines an unique molecular subtype of NSCLC and that may be amenable to targeted therapy [ 15 , 16 ]. The TAT for the MI Tumor Seek Hybrid TM test for the five cases varied from 10 to 21 days and required 10–16 FFPE slides.…”

Section: Resultsmentioning

confidence: 99%

Efficient Lung Cancer Molecular Diagnostics by Combining Next Generation Sequencing with Reflex Idylla Genefusion Assay Testing

Nkosi,

George,

Liu

et al. 2023

Genes

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Molecular diagnostics for lung cancer is a well-established standard of care, but how to use the available diagnostic tools for optimal and cost-effective patient care remains unresolved. Here, we show that DNA-only, small gene next-generation sequencing (sNGS) panels (<50 genes) combined with ultra-rapid reflex testing for common fusion transcripts using the Idylla Genefusion assay provide a cost-effective and sufficiently comprehensive testing modality for the majority of lung cancer cases. We also demonstrate the need for additional reflex testing capability on larger DNA and fusion panels for a small subset of lung cancers bearing rare single-nucleotide variants, indels and fusion transcripts and secondary, post-treatment resistance mutations. A similar testing workflow could be adopted for other solid tumor types for which extensive gene/fusion variant profiles are available both in the treatment-naïve and post-therapy settings.

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Section: Resultsmentioning

confidence: 99%

Efficient Lung Cancer Molecular Diagnostics by Combining Next Generation Sequencing with Reflex Idylla Genefusion Assay Testing

Nkosi,

George,

Liu

et al. 2023

Genes

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“…FGFR fusions were reported for the first time in 2012, in a glioblastoma tumor; they were rarely observed (0.2%) in non-small cell lung cancer, and predominantly (but not exclusively) in squamous cell carcinomas (3% of them harboring FGFR3-TACC3 rearrangement). This is an extremely important observation, since these patients could benefit from tailored therapy [23,[25][26][27][28][29].…”

Section: Clear Cell Features In Lung Carcinomamentioning

confidence: 99%

Atypical Histopathological Aspects of Common Types of Lung Cancer—Our Experience and Literature Review

Marghescu,

Leonte,

Radu

et al. 2024

Medicina

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Lung cancer is among the most common oncological diseases regarding incidence and mortality, with most of these having epithelial origins. Pathological reporting of these tumors is conducted according to the 5th edition of the World Health Organisation (WHO) classification of thoracic tumours. This study aims to draw the pathologist’s attention to four rare, atypical microscopic aspects that some of the most common types of lung malignancies reveal upon standard evaluation (hematoxylin-eosin stain) that make histopathological diagnosis challenging: acantholytic, pseudoangiosarcomatous, signet ring cell, and clear cell features. Each of these aspects was exemplified by a case diagnosed in the pathology department of the “Marius Nasta” Institute. Furthermore, we analyzed the classification dynamics of different WHO editions and used PubMed to review articles written in English and published in the last eleven years on this subject. Pathologists should be familiar with these unusual aspects to avoid misdiagnoses and to ensure the correct classification of tumors, which is extremely important because these tumor phenotypes have been associated with specific molecular alterations and a worse clinical evolution. There is a need to clarify the histogenesis and associated genetic mutations, given the fact that the rarity of these tumor phenotypes makes their study difficult. Some authors consider these to be overlapping entities; however, we do not encourage this, as they may exhibit different prognoses and various molecular alterations with important therapeutic implications. The signet ring cell feature was associated with ALK rearrangement in lung adenocarcinoma; thus, these patients can benefit from tailored therapy with ALK-tyrosine kinase inhibitors (ALK-TKI). Recent studies associated clear cell morphology with FGFR3-TACC3 fusion, suggesting that patients with this diagnosis may be potentially eligible for FGFR inhibitors. We described, for the first time, the pseudoangiosarcomatous pattern in a case of lung adenocarcinoma; to our knowledge this aspect has only been described until now in the context of squamous cell carcinomas.

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“…For example, mutations in the extracellular region of FGFR2 and FGFR3 in LSCC samples have been shown to drive cellular transformation and respond to FGFR inhibition in preclinical settings ( 28 ). Recently, a patient with LSCC who had an FGFR3-TACC3 gene fusion was successfully treated and retreated with erdafitinib ( 29 ). FGFR3-TACC3 gene fusions have also emerged as a potential mechanism of resistance to EGFR inhibitors ( 30 ).…”

Section: Perspectives Of Fgfr Inhibition In Lsccmentioning

confidence: 99%

Genomic insights into the mechanisms of FGFR1 dependency in squamous cell lung cancer

Mäkinen,

Meyerson

2023

Journal of Clinical Investigation

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Although subsets of patients with lung squamous cell carcinoma (LSCC) benefit from immunotherapy, there are few effective molecularly targeted treatments for LSCC. Fibroblast growth factor receptor (FGFR) inhibitors provide a therapeutic option for patients with LSCC harboring FGFR aberrations, but their therapeutic efficacy has been limited to date. In this issue of the JCI , Malchers et al. identified tail-to-tail rearrangements, either within or near FGFR1 , that are associated with FGFR1 dependency and sensitivity to FGFR inhibition in LSCC. These results may help improve the selection of patients with LSCC who are most likely to benefit from treatment with FGFR inhibitors.

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Successful Treatment and Retreatment With Erdafitinib for a Patient With FGFR3-TACC3 Fusion Squamous NSCLC: A Case Report

Cited by 4 publications

References 10 publications

Efficient Lung Cancer Molecular Diagnostics by Combining Next Generation Sequencing with Reflex Idylla Genefusion Assay Testing

Efficient Lung Cancer Molecular Diagnostics by Combining Next Generation Sequencing with Reflex Idylla Genefusion Assay Testing

Atypical Histopathological Aspects of Common Types of Lung Cancer—Our Experience and Literature Review

Genomic insights into the mechanisms of FGFR1 dependency in squamous cell lung cancer

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