Metadata supporting the article: Impressive response to combination dabrafenib, trametinib, and osimertinib in a metastatic EGFR-mutant/BRAF V600E lung adenocarcinoma patient
Creators: name: Ribeiro, Maurício Fernando Silva Almeida
name: Franciele Hinterholz Knebel
name: Bettoni, Fabiana
name: Saddi, Rodrigo
name: Sacardo, Karina Perez
name: Canedo, Felipe Sales Nogueira Amorim
name: Alessi, João Victor Machado
name: Shimada, Andrea Kazumi
name: Marin, José Flávio Gomes
name: Camargo, Anamaria Aranha
name: Katz, Artur
Publisher: name: figshare
Year: 2021
Subjects: subject: Biological Techniques
subject: 69999 Biological Sciences not elsewhere classified
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Cancer
subject: Biomarkers
subject: Medicine
subject: 111203 Cancer Genetics
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: 111204 Cancer Therapy (excl. Chemotherapy and Radiation Therapy)

description: The use of osimertinib to target epidermal growth factor receptor (EGFR) has become the standard of care in untreated EGFR-mutant non–small cell lung cancer (NSCLC) patients. Although osimertinib can be highly active, showing more durable outcomes than first-generation tyrosine kinase inhibitors (TKI), most tumors invariably become resistant, limiting its long-term clinical benefit. The present study is a case report that describes the treatment of a 50 year-old man diagnosed with a stage IV lung adenocarcinoma harbouring an EGFR activating mutation and a BRAF V600E, with dabrafenib, trametinib and osimertinib. The treatment was conducted outside a clinical trial under the patient's permission after a careful discussion regarding pros and cons of the strategy.<b><br></b><b>Data access</b>: The datasets that support the findings of this study are not publicly available in order to protect patient privacy. The data will be made available on reasonable request. For data access requests regarding the liquid biopsy (ctDNA quantification) data, please contact Dr. Franciele Knebel, email address: <b>fhknebel@mochsl.org.br</b>. For data access requests regarding the PET-CT high resolution images and PERCIST calculations, please contact Dr. José Marin, email address:<b> jfgmarin@yahoo.com.br</b>. For data access requests regarding the summary of the toxicities arising under osimertinib plus BRAF/MEK inhibition, please contact the corresponding author Dr. Maurício Ribeiro, email address: <b>mauricio.fsaribeiro@hsl.org.br</b>. <b><br></b><b>Study approval and patient consent:</b> This study was approved by Hospital Sírio-Libanês Ethics Committee (HSL-RC2020-16). The patient provided written informed consent for blood collection and ctDNA analysis.<br><b>Study aims and methodology</b>: Increased understanding of the relationship of concurring genomic alterations in EGFR-mutant NSCLC may enable new therapeutic opportunities upon disease progression to osimertinib. In this case report, response to dabrafenib, trametinib and osimertinib treatment was monitored, in a metastatic lung cancer patient harboring EGFR E746_A750del, BRAF V600E and PIK3CA E545K activating mutations. Additionally, levels of cell-free DNA (cfDNA), determine by ddPCR, were used to quantify the circulating levels of the EGFR activating mutation (EGFR E746_A750 del) and of the resistance mutations (EGFR T790M, PIK3CA E545K, and BRAF V600E).A 50-year-old non-smoker man was diagnosed with a tubule-papillary lung adenocarcinoma metastatic to bones and soft tissue (stage IVB - AJCC 8th edition) in July 2016. Several hypermetabolic bone lesions were observed on staging 18- fluorodeoxyglucose positron-emission tomography (18F-FDG PET-CT) scan at diagnosis. A baseline Next Generation Sequencing (NGS) assay (TruSightTumor™ -Illumina®) of soft tissue metastasis revealed the presence of an activating EGFR exon 19 deletion (EGFR E746_A750del). No concurrent alterations in BRAF or in PIK3CA were identified at that time.Serial blood samples were collected between May 2017 and April 2020. Peripheral blood (20ml) was collected into tubes containing EDTA. Plasma was separated from the blood within 2 hours of blood collection. cfDNA was extracted using QIAamp MinElute Virus Vacuum Kit (Qiagen, Hilden, Germany) and stored at −80 °C.Cell-free DNA (cfDNA) was quantified using the RNase P Copy Number Reference Assay (Life Technologies, Carlsbad, California). A total of 3000 genomeequivalents (~10ng of cfDNA) were analyzed per assay to achieve a detection sensitivity of 0.2%. ddPCR was performed on the QX200 Droplet Digital PCR System, and data were analysed using QuantaSoft software (Bio-Rad).For more details on the methodology and patient clinical characteristics, please refer to the related article.<br><b>Datasets supporting the findings of the study: </b><br>Data supporting figure 1: <b>Liquid Biopsy_data.xlsx</b>, in .xlsx file format. The data file includes ctDNA levels in serial plasma samples based on fractional abundance of EGFR T790M, EGFR del19 (E746_A750 del), BRAF V600E and PIK3CA E545K mutations.<br>Data supporting figure 2: <b>PERCIST_images.pptx</b>, is in .pptx file format and contains PERCIST calculation data and PET-CT high resolution key images.<br>Data supporting table 1: <b>Toxicity_DTO_literature.xlsx</b>, is in .xlsx file format, and contains a brief summary of the literature regarding toxicities arising under osimertinib plus BRAF/MEK inhibition. Cited articles are already available in the literature and are included in the references of the related article.<br>