Personalized Therapy in a Patient With EGFR-Mutated NSCLC Developing Sequential CCDC6-RET Fusion and BRAF V600E Mutation as Bypass Resistance Mechanisms
In this case report, we describe a case of sequential acquired CCDC6-RET fusion and BRAF V600E mutation observed in a patient with EGFR-mutated NSCLC treated with osimertinib and with combined selpercatinib and osimertinib. The discovery of genomic resistance mechanisms was facilitated by serial liq...
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Elsevier
2025-03-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364324001437 |
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| author | Arianna Marinello, MD Claudia Parisi, MD Damien Vasseur, PhD David Combarel, PharmD Juliette Bihoreau, NP Pernelle Lavaud, MD Rémy Ezzedine, MD Lodovica Zullo, MD Luc Friboulet, PhD Gerard Zalcman, MD, PhD Antoine Italiano, MD, PhD Benjamin Besse, MD, PhD Mihaela Aldea, MD, PhD |
| author_facet | Arianna Marinello, MD Claudia Parisi, MD Damien Vasseur, PhD David Combarel, PharmD Juliette Bihoreau, NP Pernelle Lavaud, MD Rémy Ezzedine, MD Lodovica Zullo, MD Luc Friboulet, PhD Gerard Zalcman, MD, PhD Antoine Italiano, MD, PhD Benjamin Besse, MD, PhD Mihaela Aldea, MD, PhD |
| author_sort | Arianna Marinello, MD |
| collection | DOAJ |
| description | In this case report, we describe a case of sequential acquired CCDC6-RET fusion and BRAF V600E mutation observed in a patient with EGFR-mutated NSCLC treated with osimertinib and with combined selpercatinib and osimertinib. The discovery of genomic resistance mechanisms was facilitated by serial liquid and tissue biopsies and molecular tumor board discussion. After the identification of CCDC6-RET fusion, the patient received a combination of selpercatinib and osimertinib with prolonged benefit and manageable toxicity. When a novel BRAF V600E mutation was detected at progression, the molecular tumor board suggested the administration of triple therapy, adding trametinib (anti-MEK). Nevertheless, treatment was discontinued for toxicity, highlighting the challenges of using multiple drug combinations to address complex resistance. |
| format | Article |
| id | doaj-art-342ea336baed47408d1a5e3b6965bb2f |
| institution | Kabale University |
| issn | 2666-3643 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj-art-342ea336baed47408d1a5e3b6965bb2f2025-02-05T04:32:40ZengElsevierJTO Clinical and Research Reports2666-36432025-03-0163100773Personalized Therapy in a Patient With EGFR-Mutated NSCLC Developing Sequential CCDC6-RET Fusion and BRAF V600E Mutation as Bypass Resistance MechanismsArianna Marinello, MD0Claudia Parisi, MD1Damien Vasseur, PhD2David Combarel, PharmD3Juliette Bihoreau, NP4Pernelle Lavaud, MD5Rémy Ezzedine, MD6Lodovica Zullo, MD7Luc Friboulet, PhD8Gerard Zalcman, MD, PhD9Antoine Italiano, MD, PhD10Benjamin Besse, MD, PhD11Mihaela Aldea, MD, PhD12Department of Medical Oncology, International Center for Thoracic Cancers (CICT), Gustave Roussy, Villejuif, France; INSERM Unit 1030 – Molecular Radiotherapy and Therapeutic Innovation, Gustave Roussy, Villejuif, FranceDepartment of Medical Oncology, International Center for Thoracic Cancers (CICT), Gustave Roussy, Villejuif, France; Paris-Saclay University, Kremlin Bicetre, FranceMedical Biology and Pathology Department, Gustave Roussy, Villejuif, FrancePharmacology Department, Gustave Roussy, Villejuif, FranceDepartment of Medical Oncology, International Center for Thoracic Cancers (CICT), Gustave Roussy, Villejuif, FranceDepartment of Medical Oncology, International Center for Thoracic Cancers (CICT), Gustave Roussy, Villejuif, FranceThoracic Oncology Department Paris-Nord, Hospital Bichat-Claude Bernard, AP-HP, Paris, FranceDepartment of Medical Oncology, International Center for Thoracic Cancers (CICT), Gustave Roussy, Villejuif, FranceInserm U981, Gustave Roussy, Villejuif, FranceThoracic Oncology Department-CIC1425/CLIP2 Paris-Nord, Hospital Bichat-Claude Bernard, AP-HP, Université Paris-Diderot, Paris, FrancePersonalized medicine, Drug Development Department, Gustave Roussy, Villejuif, FranceDepartment of Medical Oncology, International Center for Thoracic Cancers (CICT), Gustave Roussy, Villejuif, France; Paris-Saclay University, Kremlin Bicetre, FranceDepartment of Medical Oncology, International Center for Thoracic Cancers (CICT), Gustave Roussy, Villejuif, France; Paris-Saclay University, Kremlin Bicetre, France; Corresponding author. Address for correspondence: Mihaela Aldea, MD, PhD, Department of Cancer Medicine, Thoracic Cancer Unit, Gustave Roussy, 114 Rue Edouard Vaillant, Villejuif 94805, France.In this case report, we describe a case of sequential acquired CCDC6-RET fusion and BRAF V600E mutation observed in a patient with EGFR-mutated NSCLC treated with osimertinib and with combined selpercatinib and osimertinib. The discovery of genomic resistance mechanisms was facilitated by serial liquid and tissue biopsies and molecular tumor board discussion. After the identification of CCDC6-RET fusion, the patient received a combination of selpercatinib and osimertinib with prolonged benefit and manageable toxicity. When a novel BRAF V600E mutation was detected at progression, the molecular tumor board suggested the administration of triple therapy, adding trametinib (anti-MEK). Nevertheless, treatment was discontinued for toxicity, highlighting the challenges of using multiple drug combinations to address complex resistance.http://www.sciencedirect.com/science/article/pii/S2666364324001437EGFR-mutated NSCLCRET fusionBRAF V600ESelpercatinibTrametinibCase report |
| spellingShingle | Arianna Marinello, MD Claudia Parisi, MD Damien Vasseur, PhD David Combarel, PharmD Juliette Bihoreau, NP Pernelle Lavaud, MD Rémy Ezzedine, MD Lodovica Zullo, MD Luc Friboulet, PhD Gerard Zalcman, MD, PhD Antoine Italiano, MD, PhD Benjamin Besse, MD, PhD Mihaela Aldea, MD, PhD Personalized Therapy in a Patient With EGFR-Mutated NSCLC Developing Sequential CCDC6-RET Fusion and BRAF V600E Mutation as Bypass Resistance Mechanisms JTO Clinical and Research Reports EGFR-mutated NSCLC RET fusion BRAF V600E Selpercatinib Trametinib Case report |
| title | Personalized Therapy in a Patient With EGFR-Mutated NSCLC Developing Sequential CCDC6-RET Fusion and BRAF V600E Mutation as Bypass Resistance Mechanisms |
| title_full | Personalized Therapy in a Patient With EGFR-Mutated NSCLC Developing Sequential CCDC6-RET Fusion and BRAF V600E Mutation as Bypass Resistance Mechanisms |
| title_fullStr | Personalized Therapy in a Patient With EGFR-Mutated NSCLC Developing Sequential CCDC6-RET Fusion and BRAF V600E Mutation as Bypass Resistance Mechanisms |
| title_full_unstemmed | Personalized Therapy in a Patient With EGFR-Mutated NSCLC Developing Sequential CCDC6-RET Fusion and BRAF V600E Mutation as Bypass Resistance Mechanisms |
| title_short | Personalized Therapy in a Patient With EGFR-Mutated NSCLC Developing Sequential CCDC6-RET Fusion and BRAF V600E Mutation as Bypass Resistance Mechanisms |
| title_sort | personalized therapy in a patient with egfr mutated nsclc developing sequential ccdc6 ret fusion and braf v600e mutation as bypass resistance mechanisms |
| topic | EGFR-mutated NSCLC RET fusion BRAF V600E Selpercatinib Trametinib Case report |
| url | http://www.sciencedirect.com/science/article/pii/S2666364324001437 |
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