Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2025 Jan 31;14(1):16-23.
doi: 10.21037/tcr-24-1827. Epub 2025 Jan 20.

How to select between osimertinib or afatinib in P-loop and αC-helix compressing (G719X, S768I) or classical-like (L861Q) EGFR mutations: what preclinical models and clinical data have taught us in the early 2020s

Julia M Berg #  1 , Toshiki A Kobayashi #  1 , Daniel B Costa  1
Affiliations
Editorial

How to select between osimertinib or afatinib in P-loop and αC-helix compressing (G719X, S768I) or classical-like (L861Q) EGFR mutations: what preclinical models and clinical data have taught us in the early 2020s

Julia M Berg et al. Transl Cancer Res. .
No abstract available

Keywords: Epidermal growth factor receptor (EGFR); G719X; L861Q; afatinib; osimertinib.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-1827/coif). D.B.C. reports receiving consulting fees and honoraria from Takeda/Millennium Pharmaceuticals, AstraZeneca, Pfizer, Blueprint Medicines, and Janssen, institutional research support from Takeda/Millennium Pharmaceuticals, AstraZeneca, Pfizer, Merck Sharp and Dohme, Merrimack Pharmaceuticals, Bristol Myers Squibb, Clovis Oncology, Spectrum Pharmaceuticals, Tesaro and Daiichi Sankyo, and consulting fees from Teladoc and Grand Rounds by Included Health plus royalties from Life Technologies; all outside the submitted work. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Structure-function classification of EGFR mutants and clinical outcomes of EGFR mutated lung cancers. (A) Graphical description of the tyrosine kinase domain of EGFR gene and frequency of EGFR mutations [as adapted from reference (1)] overlaying the type of mutant with the newly recognized MD Anderson Cancer Center preclinical structure-function classification of EGFR mutants for sensitivity to EGFR TKIs. (B) Summary of outcomes from clinical trials and observation cohorts of patients with EGFR mutated lung cancer treated with osimertinib, with a focus on ORR, PFS, TTF and OS. Data obtained from references (2-7). (C) Summary of outcomes from clinical trials and observation cohorts of patients with EGFR mutated lung cancer treated with afatinib, with a focus on ORR, PFS, TTF and OS. Data obtained from references (8-13). In the figure, the mutation type outcome reference indicates: 1 = reference (3), 2 = reference (4), 3 = reference (2), 4 = reference (5), 5 = reference (6), 6 = reference (7), 7 = reference (8), 8 = reference (9), 9 = reference (10), 10 = reference (11), 11 = reference (12), 12 = reference (13). One cohort of osimertinib, reference (14), was not used for (B). The MD Anderson Cancer Center structure-function classification was initially described in reference (15). In the figure, * indicates when TTF was used instead of PFS. EGFR, epidermal growth factor receptor; ORR, overall response rate; PFS, progression-free survival; TTF, time to treatment failure; OS, overall survival.
See this image and copyright information in PMC

Comment on

References

    1. Le X, Nadler E, Costa DB, et al. EGFR Tyrosine Kinase Inhibitors for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Podcast. Target Oncol 2023;18:807-17. 10.1007/s11523-023-00994-2 - DOI - PMC - PubMed
    1. Okuma Y, Kubota K, Shimokawa M, et al. First-Line Osimertinib for Previously Untreated Patients With NSCLC and Uncommon EGFR Mutations: The UNICORN Phase 2 Nonrandomized Clinical Trial. JAMA Oncol 2024;10:43-51. 10.1001/jamaoncol.2023.5013 - DOI - PMC - PubMed
    1. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med 2018;378:113-25. 10.1056/NEJMoa1713137 - DOI - PubMed
    1. Planchard D, Jänne PA, Cheng Y, et al. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med 2023;389:1935-48. 10.1056/NEJMoa2306434 - DOI - PubMed
    1. Ji J, Aredo JV, Piper-Vallillo A, et al. Osimertinib in NSCLC With Atypical EGFR-Activating Mutations: A Retrospective Multicenter Study. JTO Clin Res Rep 2023;4:100459. 10.1016/j.jtocrr.2022.100459 - DOI - PMC - PubMed

LinkOut - more resources