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Research Article|Articles in Press, 100459

Osimertinib in Non-Small Cell Lung Cancer (NSCLC) with Atypical EGFR Activating Mutations: A Retrospective Multicenter Study

Open AccessPublished:January 09, 2023DOI:https://doi.org/10.1016/j.jtocrr.2022.100459
Osimertinib in Non-Small Cell Lung Cancer (NSCLC) with Atypical EGFR Activating Mutations: A Retrospective Multicenter Study
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      ABSTRACT

      Introduction

      Epidermal growth factor receptor (EGFR) mutations drive a subset of non-small cell lung cancer (NSCLC). Patients harboring the common EGFR mutations, deletion of exon 19 (Ex19del) and L858R, respond well to osimertinib, a third-generation tyrosine kinase inhibitor. However, 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 from six US academic cancer centers were included with metastatic NSCLC treated with osimertinib, harboring at least one atypical EGFR mutation, excluding concurrent Ex19del, L858R, or T790M mutations. Baseline clinical characteristics were collected. The primary endpoint was the time to treatment discontinuation (TTD) of osimertinib. In evaluable patients, objective response rate (ORR) by RECIST 1.1 was assessed.

      Results

      Fifty NSCLC patients 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% CI, 6.5 – 12.9) overall and 10.7 months (95% CI, 3.2 – 18.1) in the first line setting (n=20). The ORR 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 months), G719X (7.8 months), and exon 20 insertion (1.5 months) mutations.

      Conclusion

      Osimertinib has activity in patients with NSCLC harboring atypical EGFR mutations. Osimertinib activity differs by the type of atypical EGFR activating mutation.

      Keywords

      Article info

      Publication history

      Accepted: December 28, 2022
      Received in revised form: December 16, 2022
      Received: October 27, 2022

      Publication stage

      In Press Journal Pre-Proof

      Footnotes

      Conflict of Interest Disclosures:

      APV reports Institutional Research Funding from Gilead and consulting fees from Sanofi-Genzyme. JR reports consulting or honoraria from Gritstone Oncology, Lilly, AstraZeneca, Takeda, Sanofi-Genzyme, Genentech, Janssen, and Guardant Health HH has served as a compensated consultant or received honoraria from Foundation Medicine, Blueprint Medicines, Takeda, AstraZeneca, Janssen, Phillips, Boehringer Ingelheim, Turning Point Therapeutics; institutional research support from Roche Sequencing Solutions, Eli Lilly Oncology, Bristol Myers Squibb. HAW reports research funding from ACEA Biosciences, Arrvs Therapeutics, AstraZeneca/Medimmune, BMS, Clovis Oncology, Genentech/Roche, Merck, Novartis, SeaGen, Xcovery, and Helsinn. She also participates on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Janessen, Daiichi Sankyo, Blueprint, Mirati, Merck, Genentch/Roche, International Association for the Study of Lung Cancer, and ECOG-ACRIN. CMB receives institutional research funding from AstraZeneca. MLW reports she is an immediate family member is an employee of Genentech with stock ownership and receives royalties from UpToDate. CM is employed by Genentech (in addition to stated UCSF affliliation). ZP reports consulting fees from AstraZeneca, Janssen, Takeda, Eli Lilly, Daiichi Sankyo, Cullinan Oncology, C4 Therapeutics and Blueprint Medicines, and research support (to institution) from Novartis, Takeda, Spectrum, AstraZeneca, Tesaro/GSK, Cullinan Oncology, Daiichi Sankyo, AbbVie, Janssen, Blueprint Medicines. JN reports grants and personal fees from Genentech/Roche, grants from Merck, grants from Novartis, grants from Boehringer Ingelheim, grants and personal fees from Exelixis, grants from Nektar Therapeutics, grants and personal fees from Takeda Pharmaceuticals, grants from Adaptimmune, grants from GSK, grants from Janssen, grants from AbbVie, grants and personal fees from AstraZeneca, personal fees from Eli Lilly and Company, personal fees from Jounce Therapeutics, personal fees from Calithera Biosciences, personal fees from Amgen, personal fees from Iovance Biotherapeutics, personal fees from Blueprint Pharmaceuticals, personal fees from Regeneron Pharmaceuticals, personal fees from Natera, personal fees from Sanofi/Regeneron, personal fees from D2G Oncology, personal fees from Surface Oncology, personal fees from Turning Point Therapeutics, personal fees from Mirati Therapeutics, personal fees from Gilead, other from CME Matters, other from Clinical Care Options, other from Research to Practice, other from Medscape, other from Biomedical Learning Institute, other from MLI Peerview, other from Prime Oncology, other from Projects in Knowledge, other from Rockpointe, other from MJH Life Sciences, other from Medical Educator Consortium, and other from HMP Education.

      Prior Presentation: Presented at the 2020 ASCO Annual Meeting, Chicago, IL June 2020

      CRediT Statement

      Jingran Ji: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Visualization, Writing - original draft, Writing - review & editing. Jacqueline V. Aredo: Investigation, Data curation, Writing - review & editing. Andrew Piper-Vallillo: Investigation, Data curation, Writing - review & editing. Laura Huppert: Investigation, Data curation, Writing - review & editing. Julia K. Rotow: Investigation, Data curation, Writing - review & editing. Hatim Husain: Investigation, Data curation, Writing - review & editing. Susan Stewart: Conceptualization, Data curation, Methodology, Writing - review & editing. Rosemary Cobb: Investigation, Data curation, Writing - review & editing. Heather A. Wakelee: Investigation, Data curation, Writing - review & editing. Collin Blakely: Investigation, Data curation, Writing - review & editing. Melisa L. Wong: Investigation, Data curation, Writing - review & editing. Matthew A. Gubens: Investigation, Data curation, Writing - review & editing. Mohammed H. Madani: Investigation, Writing - review & editing. Subba R. Digumarthy: Investigation, Writing - review & editing. Caroline McCoach: Investigation, Data curation, Writing - review & editing. Zofia Piotrowska: Investigation, Data curation, Writing - review & editing. Joel W. Neal: Investigation, Data curation, Writing - review & editing. Jonathan W. Riess: Supervision, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Visualization, Writing - original draft, Writing - review & editing.

      Identification

      DOI: https://doi.org/10.1016/j.jtocrr.2022.100459

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      © 2023 Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer.

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