A Patient with Lung Adenocarcinoma and RET Fusion Treated with Vandetanib

Gautschi, Oliver; Zander, Thilo; Keller, Franziska Aebersold; Strobel, Klaus; Hirschmann, Astrid; Aebi, Stefan; Diebold, Joachim

doi:10.1097/jto.0b013e31828a4d07

Cited by 97 publications

(63 citation statements)

References 5 publications

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“…10,11,16,17 While in 3 independent phase II trials, RET inhibitors including cabozantinib and vandetanib were used to treat a total of 7 RET fusion-positive patients of lung adenocarcinoma. 14,18,19 As a result, 4 had confirmed partial responses and 3 had prolonged stable disease, indicating the therapeutic potential of RET inhibitors as targeted drugs tailored for RET fusion-positive patients.…”

Section: Introductionmentioning

confidence: 94%

The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis

Chen

Wang

Xie

et al. 2015

Cancer Biology & Therapy

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(2015) The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis, Cancer Biology & Therapy, 16:7, 1019-1028, DOI: 10.1080/15384047.2015 Purpose. The RET fusion gene is a novel oncogene observed in a subset of NSCLC in recent years. Nevertheless, the results of epidemiological studies concerning the gene remain unclear. Thus, a meta-analysis was conducted to evaluate the correlation of RET fusion gene with demographic and clinicopathological features of NSCLC. Methods. PubMed, Embase, and Web of Science databases were searched to identify eligible studies. The association of RET fusion gene occurrence with gender, age, smoking status, histology type and tumor stage were analyzed in metaanalysis. Subgroup analysis according to patients' location (Asian and non-Asian) was also conducted. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the correlation. Results. Nine studies with a total of 6,899 NSCLC patients met the inclusion criteria. A total of 84 patients with RET fusion gene were detected. The RET fusion gene was identified at significantly higher frequencies in female (OR D 0.55, 95%CI D 0.35-0.85) than male patients and in young (<60 ) patients (OR D 0.43, 95%CI D 0.19-0.99) than old patients ( 60 ), particularly in patients from Asian. A significant higher frequency was also identified in non-smokers (OR D 0.28, 95% CI D 0.16-0.49), and in patients with lung adenocarcinomas (OR D 3.59, 95%CI D 1.50-8.56). Additionally, no association between RET fusion gene and the TNM stage of tumor was observed. Conclusion. RET fusion gene occurred predominantly in Asian females with younger age, in non-smokers, and in lung adenocarcinomas patients. This subset of NSCLC patients might be good candidates for personalized diagnostic and therapeutic approaches.

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Section: Introductionmentioning

confidence: 94%

The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis

Chen

Wang

Xie

et al. 2015

Cancer Biology & Therapy

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“…62,64e67 The potential to treat RET-positive lung cancers with inhibitors of the RET kinase is being explored in phase II clinical trials, 68,69 although small series and case reports have shown promise. 70,71 Given the rarity of RET rearrangements and limited evidence of therapeutic benefit, testing for RET alterations is not recommended as a stand-alone test for all lung adenocarcinoma patients. However, any large multigene panel test developed for lung cancer patients, either for initial workup or for patients who are wild type for EGFR, ALK, and ROS1, should include RET.…”

Section: Expert Consensus Opinionmentioning

confidence: 99%

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

Aung

Donald

Ellison

et al. 2014

The Journal of Molecular Diagnostics

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Context: In 2013, an evidence-based guideline was published by the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology to set standards for the molecular analysis of lung cancers to guide treatment decisions with targeted inhibitors. New evidence has prompted an evaluation of additional laboratory technologies, targetable genes, patient populations, and tumor types for testing. Objective: To systematically review and update the 2013 guideline to affirm its validity; to assess the evidence of new genetic discoveries, technologies, and therapies; and to issue an evidence-based update. Design: The College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology convened an expert panel to develop an evidence-based guideline to help define the key questions and literature search terms, review abstracts and full articles, and draft recommendations. Results: Eighteen new recommendations were drafted. The panel also updated 3 recommendations from the 2013 guideline. Conclusions: The 2013 guideline was largely reaffirmed with updated recommendations to allow testing of cytology samples, require improved assay sensitivity, and recommend against the use of

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“…134,135 In a recent study, Lee et al 133 showed that 16% (15 out of 94) of EGFR/KRAS/ALK triple-negative lung adenocarcinomas harboured RET rearrangement. In contrast to previous studies, 129,132 the authors demonstrated moderate-to-strong immunoreactivity for RET at IHC (clone 134100, Abcam) in all 15 RET fusion-positive cases 100% of sensitivity), while a focal staining was observed also in 10 out of 79 (12%) RET fusion-negative cases (89% of specificity).…”

Section: Trim33-ret Ncoa4-ret and Ccdc6-retmentioning

confidence: 99%

Does Immunohistochemistry Represent a Robust Alternative Technique in Determining Drugable Predictive Gene Alterations in Non-Small Cell Lung Cancer?

Rossi¹,

Ragazzi

Tamagnini³

et al. 2016

CDT

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Immunohistochemistry (IHC) is a widely-tested, low-cost and rapid ancillary technique available in all laboratories of pathology. This method is generally used for diagnostic purposes, but several studies have investigated the sensitivity and specificity of different immunohistochemical antibodies as a surrogate test in the determination of predictive biomarkers in non-small cell lung cancer (NSCLC), particularly for Epidermal Growth Factor Receptor (EGFR) gene mutations, Anaplastic Lymphoma Kinase (ALK) gene and ROS1 rearrangements. In this review, a critical examination of the works comparing the consistency of IHC expression and conventional molecular techniques to identify genetic alterations with predictive value in NSCLC is discussed.Summarizing, data on sensitivity and specificity of antibodies against ALK and ROS1 are very consistent and time is comes to trust in IHC at least as a cost-effective screening tool to identify patients with rearranged tumors in clinical practice. On the other hand, mutant-specific antibodies against EGFR demonstrate a good specificity but a low-to-fair sensitivity, then raising some cautions on their employment as robust predictive biomarkers. A brief comment on preliminary experiences with antibodies against BRAF, RET, HER2 and c-MET is also included.

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A Patient with Lung Adenocarcinoma and RET Fusion Treated with Vandetanib

Cited by 97 publications

References 5 publications

The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis

The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis

Analytical Validation of BRAF Mutation Testing from Circulating Free DNA Using the Amplification Refractory Mutation Testing System

Does Immunohistochemistry Represent a Robust Alternative Technique in Determining Drugable Predictive Gene Alterations in Non-Small Cell Lung Cancer?

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