Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study
Introduction: EGFR mutations drive a subset of NSCLC. Patients harboring the common EGFR mutations, deletion of exon 19 and L858R, respond well to osimertinib, a third-generation tyrosine kinase inhibitor. Nevertheless, the effect of osimertinib on NSCLC with atypical EGFR mutations is not well desc...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-03-01
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| Series: | JTO Clinical and Research Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666364322001849 |
| _version_ | 1827975936790757376 |
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| author | Jingran Ji, MD Jacqueline V. Aredo, MD, MS Andrew Piper-Vallillo, MD Laura Huppert, MD Julia K. Rotow, MD Hatim Husain, MD Susan Stewart, PhD Rosemary Cobb, BS Heather A. Wakelee, MD Collin M. Blakely, MD, PhD Melisa L. Wong, MD, MAS Matthew A. Gubens, MD, MS Mohammad H. Madani, MD Subba R. Digumarthy, MD Caroline McCoach, MD, PhD Zofia Piotrowska, MD, MHS Joel W. Neal, MD, PhD Jonathan W. Riess, MD, MS |
| author_facet | Jingran Ji, MD Jacqueline V. Aredo, MD, MS Andrew Piper-Vallillo, MD Laura Huppert, MD Julia K. Rotow, MD Hatim Husain, MD Susan Stewart, PhD Rosemary Cobb, BS Heather A. Wakelee, MD Collin M. Blakely, MD, PhD Melisa L. Wong, MD, MAS Matthew A. Gubens, MD, MS Mohammad H. Madani, MD Subba R. Digumarthy, MD Caroline McCoach, MD, PhD Zofia Piotrowska, MD, MHS Joel W. Neal, MD, PhD Jonathan W. Riess, MD, MS |
| author_sort | Jingran Ji, MD |
| collection | DOAJ |
| description | Introduction: EGFR mutations drive a subset of NSCLC. Patients harboring the common EGFR mutations, deletion of exon 19 and L858R, respond well to osimertinib, a third-generation tyrosine kinase inhibitor. Nevertheless, the effect of osimertinib on NSCLC with atypical EGFR mutations is not well described. This multicenter retrospective study evaluates the efficacy of osimertinib among patients with NSCLC harboring atypical EGFR mutations. Methods: Patients with metastatic NSCLC treated with osimertinib, harboring at least one atypical EGFR mutation, excluding concurrent deletion of exon 19, L858R, or T790M mutations, from six U.S. academic cancer centers were included. Baseline clinical characteristics were collected. The primary end point was the time to treatment discontinuation (TTD) of osimertinib. Objective response rate by the Response Evaluation Criteria in Solid Tumors version 1.1 was also assessed. Results: A total of 50 patients with NSCLC with uncommon EGFR mutations were identified. The most frequent EGFR mutations were L861Q (40%, n = 18), G719X (28%, n = 14), and exon 20 insertion (14%, n = 7). The median TTD of osimertinib was 9.7 months (95% confidence interval [CI]: 6.5–12.9 mo) overall and 10.7 months (95% CI: 3.2–18.1 mo) in the first-line setting (n = 20). The objective response rate was 31.7% (95% CI: 18.1%–48.1%) overall and 41.2% (95% CI: 18.4%–67.1%) in the first-line setting. The median TTD varied among patients with L861Q (17.2 mo), G719X (7.8 mo), and exon 20 insertion (1.5 mo) mutations. Conclusions: Osimertinib has activity in patients with NSCLC harboring atypical EGFR mutations. Osimertinib activity differs by the type of atypical EGFR-activating mutation. |
| first_indexed | 2024-04-09T20:19:27Z |
| format | Article |
| id | doaj.art-0cd8922ebf5946adba6b0fb71a9d9100 |
| institution | Directory Open Access Journal |
| issn | 2666-3643 |
| language | English |
| last_indexed | 2024-04-09T20:19:27Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | JTO Clinical and Research Reports |
| spelling | doaj.art-0cd8922ebf5946adba6b0fb71a9d91002023-03-31T05:55:31ZengElsevierJTO Clinical and Research Reports2666-36432023-03-0143100459Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter StudyJingran Ji, MD0Jacqueline V. Aredo, MD, MS1Andrew Piper-Vallillo, MD2Laura Huppert, MD3Julia K. Rotow, MD4Hatim Husain, MD5Susan Stewart, PhD6Rosemary Cobb, BS7Heather A. Wakelee, MD8Collin M. Blakely, MD, PhD9Melisa L. Wong, MD, MAS10Matthew A. Gubens, MD, MS11Mohammad H. Madani, MD12Subba R. Digumarthy, MD13Caroline McCoach, MD, PhD14Zofia Piotrowska, MD, MHS15Joel W. Neal, MD, PhD16Jonathan W. Riess, MD, MS17City of Hope Comprehensive Cancer Center, Duarte, California; UC Davis Comprehensive Cancer Center, Sacramento, CaliforniaStanford Cancer Institute, Stanford, CaliforniaMassachusetts General Hospital Cancer Center, Boston, MassachusettsUCSF Helen Diller Comprehensive Cancer Center, San Francisco, CaliforniaDana-Farber Cancer Institute, Boston, MassachusettsUCSD Moores Comprehensive Cancer Center, La Jolla, San Diego, CaliforniaUC Davis Comprehensive Cancer Center, Sacramento, CaliforniaMassachusetts General Hospital Cancer Center, Boston, MassachusettsStanford Cancer Institute, Stanford, CaliforniaUCSF Helen Diller Comprehensive Cancer Center, San Francisco, CaliforniaUCSF Helen Diller Comprehensive Cancer Center, San Francisco, CaliforniaUCSF Helen Diller Comprehensive Cancer Center, San Francisco, CaliforniaUC Davis Comprehensive Cancer Center, Sacramento, CaliforniaMassachusetts General Hospital Cancer Center, Boston, MassachusettsUCSF Helen Diller Comprehensive Cancer Center, San Francisco, CaliforniaMassachusetts General Hospital Cancer Center, Boston, MassachusettsStanford Cancer Institute, Stanford, CaliforniaUC Davis Comprehensive Cancer Center, Sacramento, California; Corresponding author. Address for correspondence: Jonathan W. Riess, MD, MS, UC Davis Comprehensive Cancer Center, 2279 45th Street, Sacramento, California 95817.Introduction: EGFR mutations drive a subset of NSCLC. Patients harboring the common EGFR mutations, deletion of exon 19 and L858R, respond well to osimertinib, a third-generation tyrosine kinase inhibitor. Nevertheless, the effect of osimertinib on NSCLC with atypical EGFR mutations is not well described. This multicenter retrospective study evaluates the efficacy of osimertinib among patients with NSCLC harboring atypical EGFR mutations. Methods: Patients with metastatic NSCLC treated with osimertinib, harboring at least one atypical EGFR mutation, excluding concurrent deletion of exon 19, L858R, or T790M mutations, from six U.S. academic cancer centers were included. Baseline clinical characteristics were collected. The primary end point was the time to treatment discontinuation (TTD) of osimertinib. Objective response rate by the Response Evaluation Criteria in Solid Tumors version 1.1 was also assessed. Results: A total of 50 patients with NSCLC with uncommon EGFR mutations were identified. The most frequent EGFR mutations were L861Q (40%, n = 18), G719X (28%, n = 14), and exon 20 insertion (14%, n = 7). The median TTD of osimertinib was 9.7 months (95% confidence interval [CI]: 6.5–12.9 mo) overall and 10.7 months (95% CI: 3.2–18.1 mo) in the first-line setting (n = 20). The objective response rate was 31.7% (95% CI: 18.1%–48.1%) overall and 41.2% (95% CI: 18.4%–67.1%) in the first-line setting. The median TTD varied among patients with L861Q (17.2 mo), G719X (7.8 mo), and exon 20 insertion (1.5 mo) mutations. Conclusions: Osimertinib has activity in patients with NSCLC harboring atypical EGFR mutations. Osimertinib activity differs by the type of atypical EGFR-activating mutation.http://www.sciencedirect.com/science/article/pii/S2666364322001849OsimertinibNon–small cell lung cancerAtypical EGFR mutationL861QG719X |
| spellingShingle | Jingran Ji, MD Jacqueline V. Aredo, MD, MS Andrew Piper-Vallillo, MD Laura Huppert, MD Julia K. Rotow, MD Hatim Husain, MD Susan Stewart, PhD Rosemary Cobb, BS Heather A. Wakelee, MD Collin M. Blakely, MD, PhD Melisa L. Wong, MD, MAS Matthew A. Gubens, MD, MS Mohammad H. Madani, MD Subba R. Digumarthy, MD Caroline McCoach, MD, PhD Zofia Piotrowska, MD, MHS Joel W. Neal, MD, PhD Jonathan W. Riess, MD, MS Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study JTO Clinical and Research Reports Osimertinib Non–small cell lung cancer Atypical EGFR mutation L861Q G719X |
| title | Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study |
| title_full | Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study |
| title_fullStr | Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study |
| title_full_unstemmed | Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study |
| title_short | Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study |
| title_sort | osimertinib in nsclc with atypical egfr activating mutations a retrospective multicenter study |
| topic | Osimertinib Non–small cell lung cancer Atypical EGFR mutation L861Q G719X |
| url | http://www.sciencedirect.com/science/article/pii/S2666364322001849 |
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