Overcoming Resistance to Osimertinib by T790M Loss and C797S Acquisition Using Gefitinib in a Patient With EGFR-Mutant NSCLC: A Case Report
Limited strategies are available at disease progression on osimertinib for patients with EGFR-mutant NSCLC. The emergence of the on-target EGFR C797S mutation has been described as one of the most common mechanisms of resistance. In addition, loss of the EGFR T790M mutation has been mainly investiga...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | JTO Clinical and Research Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364322001801 |
| _version_ | 1797894658669412352 |
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| author | Diego Enrico, MD Florencia Tsou, MD Greta Catani, MD Carmen Pupareli, MD María Romina Girotti, PhD David Esteban Ulloa Alvarez, MD Federico Waisberg, MD Andrés Rodríguez, MD Roxana Reyes, MD Matías Chacón, MD Noemí Reguart, MD, PhD Claudio Martín, MD |
| author_facet | Diego Enrico, MD Florencia Tsou, MD Greta Catani, MD Carmen Pupareli, MD María Romina Girotti, PhD David Esteban Ulloa Alvarez, MD Federico Waisberg, MD Andrés Rodríguez, MD Roxana Reyes, MD Matías Chacón, MD Noemí Reguart, MD, PhD Claudio Martín, MD |
| author_sort | Diego Enrico, MD |
| collection | DOAJ |
| description | Limited strategies are available at disease progression on osimertinib for patients with EGFR-mutant NSCLC. The emergence of the on-target EGFR C797S mutation has been described as one of the most common mechanisms of resistance. In addition, loss of the EGFR T790M mutation has been mainly investigated as a resistance phenomenon to second-line osimertinib exposure. Remarkably, by studying the molecular profile at progression, it has been reported that the presence of the EGFR-sensitizing mutation, concurrently with the T790M, and C797S resulted in resistance to the current available EGFR tyrosine kinase inhibitors. Here, we report the first clinical evidence of gefitinib efficacy at EGFR exon 19 deletion/C797S mutation/T790M loss–mediated resistance to first-line osimertinib. Our findings highlight that dynamic genetic monitoring is a crucial approach in the evolution of EGFR-mutant NSCLC to understand the acquired molecular mechanisms for driving the best treatment strategy. |
| first_indexed | 2024-04-10T07:12:48Z |
| format | Article |
| id | doaj.art-4cf1881df756425180434e27468b9615 |
| institution | Directory Open Access Journal |
| issn | 2666-3643 |
| language | English |
| last_indexed | 2024-04-10T07:12:48Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj.art-4cf1881df756425180434e27468b96152023-02-26T04:28:19ZengElsevierJTO Clinical and Research Reports2666-36432023-02-0142100456Overcoming Resistance to Osimertinib by T790M Loss and C797S Acquisition Using Gefitinib in a Patient With EGFR-Mutant NSCLC: A Case ReportDiego Enrico, MD0Florencia Tsou, MD1Greta Catani, MD2Carmen Pupareli, MD3María Romina Girotti, PhD4David Esteban Ulloa Alvarez, MD5Federico Waisberg, MD6Andrés Rodríguez, MD7Roxana Reyes, MD8Matías Chacón, MD9Noemí Reguart, MD, PhD10Claudio Martín, MD11Thoracic Oncology Unit, Department of Medical Oncology, Alexander Fleming Cancer institute, Buenos Aires, Argentina; Clinical Research Unit, Department of Medical Oncology, Alexander Fleming Cancer Institute, Buenos Aires, Argentina; Corresponding author. Address for correspondence: Diego Enrico, MD, Thoracic Oncology Unit, Department of Medical Oncology, Alexander Fleming Cancer Institute, 1180 Crámer, Buenos Aires (1426), Argentina.Thoracic Oncology Unit, Department of Medical Oncology, Alexander Fleming Cancer institute, Buenos Aires, Argentina; Clinical Research Unit, Department of Medical Oncology, Alexander Fleming Cancer Institute, Buenos Aires, ArgentinaDepartment of Medical Oncology, Alexander Fleming Cancer Institute, Buenos Aires, ArgentinaThoracic Oncology Unit, Department of Medical Oncology, Alexander Fleming Cancer institute, Buenos Aires, ArgentinaUniversidad Argentina de la Empresa (UADE), Buenos Aires, ArgentinaDepartment of Radiology, Alexander Fleming Cancer Institute, Buenos Aires, ArgentinaClinical Research Unit, Department of Medical Oncology, Alexander Fleming Cancer Institute, Buenos Aires, Argentina; Department of Medical Oncology, Alexander Fleming Cancer Institute, Buenos Aires, ArgentinaClinical Research Unit, Department of Medical Oncology, Alexander Fleming Cancer Institute, Buenos Aires, Argentina; Department of Medical Oncology, Alexander Fleming Cancer Institute, Buenos Aires, ArgentinaThoracic Oncology Unit, Department of Medical Oncology, Hospital Clinic, Barcelona, SpainClinical Research Unit, Department of Medical Oncology, Alexander Fleming Cancer Institute, Buenos Aires, Argentina; Department of Medical Oncology, Alexander Fleming Cancer Institute, Buenos Aires, ArgentinaThoracic Oncology Unit, Department of Medical Oncology, Hospital Clinic, Barcelona, Spain; Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, SpainThoracic Oncology Unit, Department of Medical Oncology, Alexander Fleming Cancer institute, Buenos Aires, Argentina; Clinical Research Unit, Department of Medical Oncology, Alexander Fleming Cancer Institute, Buenos Aires, ArgentinaLimited strategies are available at disease progression on osimertinib for patients with EGFR-mutant NSCLC. The emergence of the on-target EGFR C797S mutation has been described as one of the most common mechanisms of resistance. In addition, loss of the EGFR T790M mutation has been mainly investigated as a resistance phenomenon to second-line osimertinib exposure. Remarkably, by studying the molecular profile at progression, it has been reported that the presence of the EGFR-sensitizing mutation, concurrently with the T790M, and C797S resulted in resistance to the current available EGFR tyrosine kinase inhibitors. Here, we report the first clinical evidence of gefitinib efficacy at EGFR exon 19 deletion/C797S mutation/T790M loss–mediated resistance to first-line osimertinib. Our findings highlight that dynamic genetic monitoring is a crucial approach in the evolution of EGFR-mutant NSCLC to understand the acquired molecular mechanisms for driving the best treatment strategy.http://www.sciencedirect.com/science/article/pii/S2666364322001801EGFRT790M lossOsimertinibC797SGefitinibCase report |
| spellingShingle | Diego Enrico, MD Florencia Tsou, MD Greta Catani, MD Carmen Pupareli, MD María Romina Girotti, PhD David Esteban Ulloa Alvarez, MD Federico Waisberg, MD Andrés Rodríguez, MD Roxana Reyes, MD Matías Chacón, MD Noemí Reguart, MD, PhD Claudio Martín, MD Overcoming Resistance to Osimertinib by T790M Loss and C797S Acquisition Using Gefitinib in a Patient With EGFR-Mutant NSCLC: A Case Report JTO Clinical and Research Reports EGFR T790M loss Osimertinib C797S Gefitinib Case report |
| title | Overcoming Resistance to Osimertinib by T790M Loss and C797S Acquisition Using Gefitinib in a Patient With EGFR-Mutant NSCLC: A Case Report |
| title_full | Overcoming Resistance to Osimertinib by T790M Loss and C797S Acquisition Using Gefitinib in a Patient With EGFR-Mutant NSCLC: A Case Report |
| title_fullStr | Overcoming Resistance to Osimertinib by T790M Loss and C797S Acquisition Using Gefitinib in a Patient With EGFR-Mutant NSCLC: A Case Report |
| title_full_unstemmed | Overcoming Resistance to Osimertinib by T790M Loss and C797S Acquisition Using Gefitinib in a Patient With EGFR-Mutant NSCLC: A Case Report |
| title_short | Overcoming Resistance to Osimertinib by T790M Loss and C797S Acquisition Using Gefitinib in a Patient With EGFR-Mutant NSCLC: A Case Report |
| title_sort | overcoming resistance to osimertinib by t790m loss and c797s acquisition using gefitinib in a patient with egfr mutant nsclc a case report |
| topic | EGFR T790M loss Osimertinib C797S Gefitinib Case report |
| url | http://www.sciencedirect.com/science/article/pii/S2666364322001801 |
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