Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification
Viola W Zhu,1 Alexa B Schrock,2 Siraj M Ali,2 Sai-Hong Ignatius Ou1 1Chao Family Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, University of California, Irvine School of Medicine, Orange, CA, USA; 2Clinical Development, Foundation Medicine, Inc., Cambridge, MA...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2019-03-01
|
| Series: | Lung Cancer: Targets and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/differential-response-to-a-combination-of-full-dose-osimertinib-and-cr-peer-reviewed-article-LCTT |
| _version_ | 1818346367670550528 |
|---|---|
| author | Zhu VW Schrock AB Ali SM Ou SI |
| author_facet | Zhu VW Schrock AB Ali SM Ou SI |
| author_sort | Zhu VW |
| collection | DOAJ |
| description | Viola W Zhu,1 Alexa B Schrock,2 Siraj M Ali,2 Sai-Hong Ignatius Ou1 1Chao Family Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, University of California, Irvine School of Medicine, Orange, CA, USA; 2Clinical Development, Foundation Medicine, Inc., Cambridge, MA, USA Abstract: Exploring resistance mechanisms in patients with EGFR-mutant non-small-cell lung cancer (NSCLC) upon disease progression on EGFR tyrosine kinase inhibitors (TKIs) has been an area of great interest as it may lead to effective next-line treatment strategies. Here we report a case of emergent MET amplification detected in a tumor sample from a patient with NSCLC harboring EGFR L858R mutation after disease progression on erlotinib. The patient subsequently had a sustained partial response to a combination of full-dose osimertinib and crizotinib with excellent tolerance but eventually had central nervous system (CNS) progression. Comprehensive genomic profiling performed on the resected brain sample continued to demonstrate MET amplification as an acquired resistance mechanism. A review of literature shows several groups have utilized similar combination regimens (erlotinib or osimertinib + crizotinib or cabozantinib), albeit with various dosing to target MET alterations in patients with EGFR-mutant NSCLC. As more actionable resistance mechanisms are identified, we envision combination TKI therapy will be readily adopted in clinical practice. Our case report adds to a growing body of evidence that combination osimertinib and crizotinib should be recommended to EGFR-mutant NSCLC patients with emergent MET amplification as acquired resistance. More importantly, as crizotinib has limited brain penetration, developing next-generation MET inhibitors with better CNS activity is urgently needed. Keywords: resistance, TKI, erlotinib, cabozantinib, CGP, gefitinib |
| first_indexed | 2024-12-13T17:17:09Z |
| format | Article |
| id | doaj.art-92497f75a8b94fb7b5a39d98c3997684 |
| institution | Directory Open Access Journal |
| issn | 1179-2728 |
| language | English |
| last_indexed | 2024-12-13T17:17:09Z |
| publishDate | 2019-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Lung Cancer: Targets and Therapy |
| spelling | doaj.art-92497f75a8b94fb7b5a39d98c39976842022-12-21T23:37:24ZengDove Medical PressLung Cancer: Targets and Therapy1179-27282019-03-01Volume 10212644534Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplificationZhu VWSchrock ABAli SMOu SIViola W Zhu,1 Alexa B Schrock,2 Siraj M Ali,2 Sai-Hong Ignatius Ou1 1Chao Family Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, University of California, Irvine School of Medicine, Orange, CA, USA; 2Clinical Development, Foundation Medicine, Inc., Cambridge, MA, USA Abstract: Exploring resistance mechanisms in patients with EGFR-mutant non-small-cell lung cancer (NSCLC) upon disease progression on EGFR tyrosine kinase inhibitors (TKIs) has been an area of great interest as it may lead to effective next-line treatment strategies. Here we report a case of emergent MET amplification detected in a tumor sample from a patient with NSCLC harboring EGFR L858R mutation after disease progression on erlotinib. The patient subsequently had a sustained partial response to a combination of full-dose osimertinib and crizotinib with excellent tolerance but eventually had central nervous system (CNS) progression. Comprehensive genomic profiling performed on the resected brain sample continued to demonstrate MET amplification as an acquired resistance mechanism. A review of literature shows several groups have utilized similar combination regimens (erlotinib or osimertinib + crizotinib or cabozantinib), albeit with various dosing to target MET alterations in patients with EGFR-mutant NSCLC. As more actionable resistance mechanisms are identified, we envision combination TKI therapy will be readily adopted in clinical practice. Our case report adds to a growing body of evidence that combination osimertinib and crizotinib should be recommended to EGFR-mutant NSCLC patients with emergent MET amplification as acquired resistance. More importantly, as crizotinib has limited brain penetration, developing next-generation MET inhibitors with better CNS activity is urgently needed. Keywords: resistance, TKI, erlotinib, cabozantinib, CGP, gefitinibhttps://www.dovepress.com/differential-response-to-a-combination-of-full-dose-osimertinib-and-cr-peer-reviewed-article-LCTTosimertinibcrizotinibEGFRMETamplificationerlotinib (3-6) |
| spellingShingle | Zhu VW Schrock AB Ali SM Ou SI Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification Lung Cancer: Targets and Therapy osimertinib crizotinib EGFR MET amplification erlotinib (3-6) |
| title | Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification |
| title_full | Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification |
| title_fullStr | Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification |
| title_full_unstemmed | Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification |
| title_short | Differential response to a combination of full-dose osimertinib and crizotinib in a patient with EGFR-mutant non-small cell lung cancer and emergent MET amplification |
| title_sort | differential response to a combination of full dose osimertinib and crizotinib in a patient with egfr mutant non small cell lung cancer and emergent met amplification |
| topic | osimertinib crizotinib EGFR MET amplification erlotinib (3-6) |
| url | https://www.dovepress.com/differential-response-to-a-combination-of-full-dose-osimertinib-and-cr-peer-reviewed-article-LCTT |
| work_keys_str_mv | AT zhuvw differentialresponsetoacombinationoffulldoseosimertinibandcrizotinibinapatientwithegfrmutantnonsmallcelllungcancerandemergentmetamplification AT schrockab differentialresponsetoacombinationoffulldoseosimertinibandcrizotinibinapatientwithegfrmutantnonsmallcelllungcancerandemergentmetamplification AT alism differentialresponsetoacombinationoffulldoseosimertinibandcrizotinibinapatientwithegfrmutantnonsmallcelllungcancerandemergentmetamplification AT ousi differentialresponsetoacombinationoffulldoseosimertinibandcrizotinibinapatientwithegfrmutantnonsmallcelllungcancerandemergentmetamplification |