Clinicopathological Characteristics of RET Rearranged Lung Cancer in European Patients

Michels, Sebastian; Scheel, Andreas H.; Scheffler, Matthias; Schultheis, Anne M.; Gautschi, Oliver; Aebersold, Franziska; Diebold, Joachim; Pall, Georg; Rothschild, Sacha I.; Bubendorf, Lukas; Hartmann, Wolfgang; Heukamp, Lukas C.; Schildhaus, Hans–Ulrich; Fassunke, Jana; Ihle, Michaela A.; Künstlinger, Helen; Heydt, Carina; Fischer, Rieke; Nogová, Lucia; Mattonet, Christian; Hein, Rebecca; Adams, Anne; Gerigk, Ulrich; Schulte, Wolfgang; Lüders, H; Grohé, Christian; Graeven, Ullrich; Müller-Naendrup, Clemens; Draube, Andreas; Kambartel, K; Krüger, Stefan; Schulze-Olden, Susanne; Serke, Monika; Engel-Riedel, Walburga; Kaminsky, Britta; Randerath, Winfried; Merkelbach‐Bruse, Sabine; Büttner, Reinhard; Wolf, Jürgen

doi:10.1016/j.jtho.2015.09.016

Cited by 67 publications

(43 citation statements)

References 13 publications

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“…A patient with metastatic PTC experienced durable stable disease following surgical excision of a cutaneous manifestation harboring a CCDC6‐RET fusion and vandetanib treatment . Additionally, partial responses have been reported in patients with RET ‐rearranged NSCLC treated with cabozantinib . Preclinical studies demonstrated that cells transformed by KIF5B ‐ RET are sensitive to treatment with vandetanib, sorafenib, and sunitinib .…”

Section: Discussionmentioning

confidence: 99%

Pediatric, Adolescent, and Young Adult Thyroid Carcinoma Harbors Frequent and Diverse Targetable Genomic Alterations, Including Kinase Fusions

et al. 2017

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Background. Thyroid carcinoma, which is rare in pediatric patients (age 0-18 years) but more common in adolescent and young adult (AYA) patients (age 15-39 years), carries the potential for morbidity and mortality. Methods. Hybrid-capture-based comprehensive genomic profiling (CGP) was performed prospectively on 512 consecutively submitted thyroid carcinomas, including 58 from pediatric and AYA (PAYA) patients, to identify genomic alterations (GAs), including base substitutions, insertions/deletions, copy number alterations, and rearrangements. This PAYA data series includes 41 patients with papillary thyroid carcinoma (PTC), 3 with anaplastic thyroid carcinoma (ATC), and 14 with medullary thyroid carcinoma (MTC). Results. GAs were detected in 93% (54/58) of PAYA cases, with a mean of 1.4 GAs per case. In addition to BRAF V600E mutations,

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Section: Discussionmentioning

confidence: 99%

Pediatric, Adolescent, and Young Adult Thyroid Carcinoma Harbors Frequent and Diverse Targetable Genomic Alterations, Including Kinase Fusions

et al. 2017

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“…29,33 ALK, ROS1, and RET were tested for rearrangement by break-apart FISH. 34,35 FISH was performed according to local screening algorithms: FGFR1 screening was performed for squamous cell carcinoma (SqCC) routinely. Starting in June 2014, MET amplification was determined in all patients with the adenocarcinoma (ADC) subtype of NSCLC.…”

Section: Fishmentioning

confidence: 99%

K-ras Mutation Subtypes in NSCLC and Associated Co-occuring Mutations in Other Oncogenic Pathways

Scheffler

Ihle

Hein

et al. 2019

Journal of Thoracic Oncology

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195

139

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“…9 These are found in 1–2% of unselected lung cancers and tend to be mutually exclusive with other lung cancer drivers. 3 Patients with RET -rearranged lung cancers are commonly never smokers or have a minimal history of prior tobacco exposure.…”

Section: Introductionmentioning

confidence: 99%

Cabozantinib in patients with advanced RET -rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial

Drilon

Rekhtman

Arcila

et al. 2016

The Lancet Oncology

381

298

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SUMMARY Background RET rearrangements are found in 1–2% of non-small cell lung cancers. Cabozantinib is a multikinase RET inhibitor that produced a 10% response rate in unselected patients with lung cancers. To evaluate the activity of cabozantinib in patients with RET-rearranged lung cancers, we conducted a prospective phase 2 trial in this molecular subgroup. Methods We enrolled patients in this open-label, Simon two-stage, phase 2 trial if they met the following criteria: metastatic or unresectable lung cancer harboring a RET rearrangement, Karnofsky performance status of >70%, and measurable disease. Cabozantinib was administered at 60 mg daily. The primary objective was to determine the overall response rate (RECIST v1·1). This analysis was performed in an intent to treat fashion in patients who received at least one dose of cabozantinib and underwent imaging performed at baseline and at least one protocol-specified follow up time point. The secondary objectives were to determine progression-free survival, overall survival, and toxicity. The accrual of RET-rearranged lung cancer patients to this protocol has been completed. This study was registered with ClinicalTrials.gov, number NCT01639508. Findings Twenty six patients with RET-rearranged lung adenocarcinomas were treated with cabozantinib. KIF5B-RET was the predominant fusion type identified in 16 (62%) patients. The study met its primary endpoint with confirmed partial responses observed in seven of 25 response-evaluable patients (overall response rate 28% [95% CI 12–49%]). The most common grade 3 treatment-related adverse events were asymptomatic lipase elevation in four patients (15%), increased alanine aminotransferase in two patients (8%), increased aspartate aminotransferase in two patients (8%), thrombocytopenia in two patients (8%), and hypophosphatemia in two patients (8%). No drug-related deaths were observed. Nineteen patients (73%) required dose reduction due to drug-related adverse events. Interpretation The observed activity of cabozantinib in patients with RET-rearranged lung cancers defines RET rearrangements as actionable drivers in patients with lung cancers. An improved understanding of tumor biology and novel therapeutic approaches will be required to improve outcomes with RET-directed targeted therapy.

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Clinicopathological Characteristics of RET Rearranged Lung Cancer in European Patients

Abstract: Patients with RET rearranged adenocarcinomas represent a rare and heterogeneous NSCLC subgroup. In some contrast to published data, we see a high prevalence of current and former smokers in our white RET cohort. The significance of co-occurring aberrations, so far, is unclear.

Cited by 67 publications

References 13 publications

Pediatric, Adolescent, and Young Adult Thyroid Carcinoma Harbors Frequent and Diverse Targetable Genomic Alterations, Including Kinase Fusions

Pediatric, Adolescent, and Young Adult Thyroid Carcinoma Harbors Frequent and Diverse Targetable Genomic Alterations, Including Kinase Fusions

K-ras Mutation Subtypes in NSCLC and Associated Co-occuring Mutations in Other Oncogenic Pathways

Cabozantinib in patients with advanced RET -rearranged non-small-cell lung cancer: an open-label, single-centre, phase 2, single-arm trial

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