Induction EGFR tyrosine kinase inhibitors prior to definitive chemoradiotherapy in unresectable stage III EGFR-mutated non-small cell lung cancer
Introduction: Increasing evidence suggests that consolidation durvalumab confers limited benefits for patients with stage III EGFR-mutated NSCLC. Induction or maintenance EGFR tyrosine kinase inhibitors (TKIs) added to concurrent chemoradiotherapy (CRT) may optimize definitive treatment, but there a...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-01-01
|
| Series: | Cancer Treatment and Research Communications |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468294222001502 |
| _version_ | 1811188535312515072 |
|---|---|
| author | Jacqueline V. Aredo Heather A. Wakelee Angela Bik-Yu Hui Sukhmani K. Padda Nitin D. Joshi H. Henry Guo Aadel Chaudhuri Maximilian Diehn Billy W. Loo, Jr. Joel W. Neal |
| author_facet | Jacqueline V. Aredo Heather A. Wakelee Angela Bik-Yu Hui Sukhmani K. Padda Nitin D. Joshi H. Henry Guo Aadel Chaudhuri Maximilian Diehn Billy W. Loo, Jr. Joel W. Neal |
| author_sort | Jacqueline V. Aredo |
| collection | DOAJ |
| description | Introduction: Increasing evidence suggests that consolidation durvalumab confers limited benefits for patients with stage III EGFR-mutated NSCLC. Induction or maintenance EGFR tyrosine kinase inhibitors (TKIs) added to concurrent chemoradiotherapy (CRT) may optimize definitive treatment, but there are limited data supporting an induction TKI strategy. Methods: We evaluated the efficacy and safety of induction EGFR TKIs administered before concurrent CRT in a retrospective series of patients with unresectable locally advanced EGFR-mutated NSCLC. Circulating tumor DNA (ctDNA) analysis was performed on a patient subset using CAPP-seq and correlated with outcomes. Results: Of six patients, three received erlotinib and three osimertinib as induction therapy before CRT. Induction TKIs were administered for a median of 2.5 months. The objective response rate after induction TKI was 83%. One patient had a complete response to induction erlotinib and continued erlotinib for 4 years until local progression, which was treated with CRT. Two patients completed maintenance erlotinib after CRT, and another received consolidation durvalumab. After a median follow-up of 20.5 months, only one patient developed disease recurrence, with rising ctDNA coinciding with recurrence. ctDNA remained undetectable in patients without recurrence, or low-level in a patient receiving maintenance erlotinib. Adverse events were mild and expected, and none developed pneumonitis. Conclusion: Induction EGFR TKI before CRT may achieve high disease control rates with promising signs of durability in patients with locally advanced EGFR-mutated NSCLC. ctDNA analysis after CRT can correlate well with clinical outcomes. Prospective studies are needed to define the role of induction EGFR TKIs in this setting. |
| first_indexed | 2024-04-11T14:20:23Z |
| format | Article |
| id | doaj.art-cc3b606db7f945f2b1fb4721c7598e52 |
| institution | Directory Open Access Journal |
| issn | 2468-2942 |
| language | English |
| last_indexed | 2024-04-11T14:20:23Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cancer Treatment and Research Communications |
| spelling | doaj.art-cc3b606db7f945f2b1fb4721c7598e522022-12-22T04:19:04ZengElsevierCancer Treatment and Research Communications2468-29422022-01-0133100659Induction EGFR tyrosine kinase inhibitors prior to definitive chemoradiotherapy in unresectable stage III EGFR-mutated non-small cell lung cancerJacqueline V. Aredo0Heather A. Wakelee1Angela Bik-Yu Hui2Sukhmani K. Padda3Nitin D. Joshi4H. Henry Guo5Aadel Chaudhuri6Maximilian Diehn7Billy W. Loo, Jr.8Joel W. Neal9Department of Medicine, University of California, San Francisco, CA, 94143, USA; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94305, USADivision of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94305, USADepartment of Radiation Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94305, USADivision of Oncology, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USAUniversity Healthcare Alliance, Stanford Healthcare, Newark, CA, 94560, USADepartment of Radiology, Stanford University School of Medicine, Stanford, CA, 94305, USADepartment of Radiation Oncology, Washington University School of Medicine in St. Louis, St. Louis, MO, 63110, USADepartment of Radiation Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94305, USADepartment of Radiation Oncology, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94305, USADivision of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA; Corresponding author at: Department of Medicine, Division of Oncology, Stanford Cancer Institute, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, CA, 94305, USA.Introduction: Increasing evidence suggests that consolidation durvalumab confers limited benefits for patients with stage III EGFR-mutated NSCLC. Induction or maintenance EGFR tyrosine kinase inhibitors (TKIs) added to concurrent chemoradiotherapy (CRT) may optimize definitive treatment, but there are limited data supporting an induction TKI strategy. Methods: We evaluated the efficacy and safety of induction EGFR TKIs administered before concurrent CRT in a retrospective series of patients with unresectable locally advanced EGFR-mutated NSCLC. Circulating tumor DNA (ctDNA) analysis was performed on a patient subset using CAPP-seq and correlated with outcomes. Results: Of six patients, three received erlotinib and three osimertinib as induction therapy before CRT. Induction TKIs were administered for a median of 2.5 months. The objective response rate after induction TKI was 83%. One patient had a complete response to induction erlotinib and continued erlotinib for 4 years until local progression, which was treated with CRT. Two patients completed maintenance erlotinib after CRT, and another received consolidation durvalumab. After a median follow-up of 20.5 months, only one patient developed disease recurrence, with rising ctDNA coinciding with recurrence. ctDNA remained undetectable in patients without recurrence, or low-level in a patient receiving maintenance erlotinib. Adverse events were mild and expected, and none developed pneumonitis. Conclusion: Induction EGFR TKI before CRT may achieve high disease control rates with promising signs of durability in patients with locally advanced EGFR-mutated NSCLC. ctDNA analysis after CRT can correlate well with clinical outcomes. Prospective studies are needed to define the role of induction EGFR TKIs in this setting.http://www.sciencedirect.com/science/article/pii/S2468294222001502EGFR mutationConcurrent chemoradiotherapyOsimertinibErlotinibInduction EGFR TKI |
| spellingShingle | Jacqueline V. Aredo Heather A. Wakelee Angela Bik-Yu Hui Sukhmani K. Padda Nitin D. Joshi H. Henry Guo Aadel Chaudhuri Maximilian Diehn Billy W. Loo, Jr. Joel W. Neal Induction EGFR tyrosine kinase inhibitors prior to definitive chemoradiotherapy in unresectable stage III EGFR-mutated non-small cell lung cancer Cancer Treatment and Research Communications EGFR mutation Concurrent chemoradiotherapy Osimertinib Erlotinib Induction EGFR TKI |
| title | Induction EGFR tyrosine kinase inhibitors prior to definitive chemoradiotherapy in unresectable stage III EGFR-mutated non-small cell lung cancer |
| title_full | Induction EGFR tyrosine kinase inhibitors prior to definitive chemoradiotherapy in unresectable stage III EGFR-mutated non-small cell lung cancer |
| title_fullStr | Induction EGFR tyrosine kinase inhibitors prior to definitive chemoradiotherapy in unresectable stage III EGFR-mutated non-small cell lung cancer |
| title_full_unstemmed | Induction EGFR tyrosine kinase inhibitors prior to definitive chemoradiotherapy in unresectable stage III EGFR-mutated non-small cell lung cancer |
| title_short | Induction EGFR tyrosine kinase inhibitors prior to definitive chemoradiotherapy in unresectable stage III EGFR-mutated non-small cell lung cancer |
| title_sort | induction egfr tyrosine kinase inhibitors prior to definitive chemoradiotherapy in unresectable stage iii egfr mutated non small cell lung cancer |
| topic | EGFR mutation Concurrent chemoradiotherapy Osimertinib Erlotinib Induction EGFR TKI |
| url | http://www.sciencedirect.com/science/article/pii/S2468294222001502 |
| work_keys_str_mv | AT jacquelinevaredo inductionegfrtyrosinekinaseinhibitorspriortodefinitivechemoradiotherapyinunresectablestageiiiegfrmutatednonsmallcelllungcancer AT heatherawakelee inductionegfrtyrosinekinaseinhibitorspriortodefinitivechemoradiotherapyinunresectablestageiiiegfrmutatednonsmallcelllungcancer AT angelabikyuhui inductionegfrtyrosinekinaseinhibitorspriortodefinitivechemoradiotherapyinunresectablestageiiiegfrmutatednonsmallcelllungcancer AT sukhmanikpadda inductionegfrtyrosinekinaseinhibitorspriortodefinitivechemoradiotherapyinunresectablestageiiiegfrmutatednonsmallcelllungcancer AT nitindjoshi inductionegfrtyrosinekinaseinhibitorspriortodefinitivechemoradiotherapyinunresectablestageiiiegfrmutatednonsmallcelllungcancer AT hhenryguo inductionegfrtyrosinekinaseinhibitorspriortodefinitivechemoradiotherapyinunresectablestageiiiegfrmutatednonsmallcelllungcancer AT aadelchaudhuri inductionegfrtyrosinekinaseinhibitorspriortodefinitivechemoradiotherapyinunresectablestageiiiegfrmutatednonsmallcelllungcancer AT maximiliandiehn inductionegfrtyrosinekinaseinhibitorspriortodefinitivechemoradiotherapyinunresectablestageiiiegfrmutatednonsmallcelllungcancer AT billywloojr inductionegfrtyrosinekinaseinhibitorspriortodefinitivechemoradiotherapyinunresectablestageiiiegfrmutatednonsmallcelllungcancer AT joelwneal inductionegfrtyrosinekinaseinhibitorspriortodefinitivechemoradiotherapyinunresectablestageiiiegfrmutatednonsmallcelllungcancer |