Osimertinib and Capmatinib Combination Therapy to Overcome MET Y1003N-Mediated Resistance in EGFR-Mutant NSCLC: A Case Report
Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is the frontline standard in the treatment of metastatic EGFR-mutant NSCLC. Although osimertinib is effective, disease progression occurs in virtually all patients, mediated by a heterogeneous array of resistance mechanisms. Activation...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | JTO Clinical and Research Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364322001205 |
| _version_ | 1811197017363316736 |
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| author | Molly Wilgucki, DO Vincent Yeung, MD Grace Ho, MD Gabriela L. Bravo Montenegro, MD Greg Jones Joshua E. Reuss, MD Stephen V. Liu, MD Chul Kim, MD, MPH |
| author_facet | Molly Wilgucki, DO Vincent Yeung, MD Grace Ho, MD Gabriela L. Bravo Montenegro, MD Greg Jones Joshua E. Reuss, MD Stephen V. Liu, MD Chul Kim, MD, MPH |
| author_sort | Molly Wilgucki, DO |
| collection | DOAJ |
| description | Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is the frontline standard in the treatment of metastatic EGFR-mutant NSCLC. Although osimertinib is effective, disease progression occurs in virtually all patients, mediated by a heterogeneous array of resistance mechanisms. Activation of the MET signaling pathway by means of amplification has been implicated in resistance to osimertinib, but activation caused by point mutations in MET has not been well described.Here, we present the case of a 65-year-old female with metastatic EGFR-mutant NSCLC whose disease progressed on osimertinib owing to emergence of MET Y1003N mutation. She subsequently received capmatinib in combination with osimertinib and achieved a partial response. This case illustrates a potential role for dual EGFR/MET inhibition in EGFR-mutated NSCLC with resistance driven by activating MET mutations. |
| first_indexed | 2024-04-12T01:08:04Z |
| format | Article |
| id | doaj.art-9d3591ef52d14726b8aabbb45542a674 |
| institution | Directory Open Access Journal |
| issn | 2666-3643 |
| language | English |
| last_indexed | 2024-04-12T01:08:04Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj.art-9d3591ef52d14726b8aabbb45542a6742022-12-22T03:54:11ZengElsevierJTO Clinical and Research Reports2666-36432022-10-01310100396Osimertinib and Capmatinib Combination Therapy to Overcome MET Y1003N-Mediated Resistance in EGFR-Mutant NSCLC: A Case ReportMolly Wilgucki, DO0Vincent Yeung, MD1Grace Ho, MD2Gabriela L. Bravo Montenegro, MD3Greg Jones4Joshua E. Reuss, MD5Stephen V. Liu, MD6Chul Kim, MD, MPH7Department of Internal Medicine, Georgetown University, Washington, District of ColumbiaLombardi Comprehensive Cancer Center, Georgetown University, Washington, District of ColumbiaLombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia; Department of Neurology, Georgetown University, Washington, District of ColumbiaLombardi Comprehensive Cancer Center, Georgetown University, Washington, District of ColumbiaInivata, Cambridge, United KingdomLombardi Comprehensive Cancer Center, Georgetown University, Washington, District of ColumbiaLombardi Comprehensive Cancer Center, Georgetown University, Washington, District of ColumbiaLombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia; Corresponding author. Address for correspondence: Chul Kim, MD, MPH, Georgetown Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, 3800 Reservoir Road Northwest, Washington, DC 20007.Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is the frontline standard in the treatment of metastatic EGFR-mutant NSCLC. Although osimertinib is effective, disease progression occurs in virtually all patients, mediated by a heterogeneous array of resistance mechanisms. Activation of the MET signaling pathway by means of amplification has been implicated in resistance to osimertinib, but activation caused by point mutations in MET has not been well described.Here, we present the case of a 65-year-old female with metastatic EGFR-mutant NSCLC whose disease progressed on osimertinib owing to emergence of MET Y1003N mutation. She subsequently received capmatinib in combination with osimertinib and achieved a partial response. This case illustrates a potential role for dual EGFR/MET inhibition in EGFR-mutated NSCLC with resistance driven by activating MET mutations.http://www.sciencedirect.com/science/article/pii/S2666364322001205NSCLCOsimertinibMETEGFRY1003NCase report |
| spellingShingle | Molly Wilgucki, DO Vincent Yeung, MD Grace Ho, MD Gabriela L. Bravo Montenegro, MD Greg Jones Joshua E. Reuss, MD Stephen V. Liu, MD Chul Kim, MD, MPH Osimertinib and Capmatinib Combination Therapy to Overcome MET Y1003N-Mediated Resistance in EGFR-Mutant NSCLC: A Case Report JTO Clinical and Research Reports NSCLC Osimertinib MET EGFR Y1003N Case report |
| title | Osimertinib and Capmatinib Combination Therapy to Overcome MET Y1003N-Mediated Resistance in EGFR-Mutant NSCLC: A Case Report |
| title_full | Osimertinib and Capmatinib Combination Therapy to Overcome MET Y1003N-Mediated Resistance in EGFR-Mutant NSCLC: A Case Report |
| title_fullStr | Osimertinib and Capmatinib Combination Therapy to Overcome MET Y1003N-Mediated Resistance in EGFR-Mutant NSCLC: A Case Report |
| title_full_unstemmed | Osimertinib and Capmatinib Combination Therapy to Overcome MET Y1003N-Mediated Resistance in EGFR-Mutant NSCLC: A Case Report |
| title_short | Osimertinib and Capmatinib Combination Therapy to Overcome MET Y1003N-Mediated Resistance in EGFR-Mutant NSCLC: A Case Report |
| title_sort | osimertinib and capmatinib combination therapy to overcome met y1003n mediated resistance in egfr mutant nsclc a case report |
| topic | NSCLC Osimertinib MET EGFR Y1003N Case report |
| url | http://www.sciencedirect.com/science/article/pii/S2666364322001205 |
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