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Introduction <p>Osimertinib is recommended, alongside afatinib, as first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) with atypical mutations in the epidermal growth factor receptor gene (<i>EGFR</i>), a population for whom real-world data are limited. We present outcomes and subsequent treatment patterns for this population in routine US practice.</p> Methods <p>Medical records from a manually curated oncology database were analyzed for adults with stage IIIB–IV NSCLC harboring atypical <i>EGFR</i> mutations, treated with first-line osimertinib (April 2018–March 2020). Data were analyzed overall and by <i>EGFR</i> mutation subgroups: compound <i>EGFR</i> mutations, comprising classical (exon [Ex] 19 deletion or L858R) and atypical (G719X, L861Q, S768I, E709X, Ex19 insertions, or Ex18–25 duplications) mutations or de novo T790M only (group A), and atypical <i>EGFR</i> mutations only (group B). Outcomes included real-world progression-free survival (rwPFS) and overall survival (OS).</p> Results <p>A total of 55 patients were included in the study (female 76%/male 24%; group A, <i>n</i> = 20; group B, <i>n</i> = 35). After a median follow-up of 11 months, median (95% confidence interval) rwPFS and OS, respectively, were 8.8 (5.5–17.2) and 28.5&#xa0;months (11.4–41.8) overall, 20.3 (10.0–44.5) and 42.5&#xa0;months (27.0–not estimable) in group A, and 6.6 (4.9–24.8) and 20.0&#xa0;months (9.2–32.9) in group B. At follow-up, 13% of patients (<i>n</i> = 7) remained on first-line osimertinib (group A, 30%; group B, 3%), 54% (<i>n</i> = 30) had discontinued due to death (group A, 40%; group B, 63%), and 33% (<i>n</i> = 18) had received subsequent treatment (group A, 30%; group B, 34%), most commonly osimertinib combinations (28%; <i>n</i> = 5).</p> Conclusions <p>First-line osimertinib may provide real-world clinical benefits for patients with advanced NSCLC with atypical <i>EGFR</i> mutations, with results suggesting greater benefit in those harboring compound <i>EGFR</i> mutations.</p>

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Real-World Outcomes and Subsequent Treatment Patterns in Patients with Advanced Non-Small Cell Lung Cancer and Atypical EGFR Mutations Receiving First-Line Osimertinib Monotherapy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月9日

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  • Jorge J. Nieva,
  • Xuejun Wang,
  • Deborah Doroshow,
  • Leslie Servidio,
  • Miranda Cooper,
  • Yan Kwan Lau,
  • Pritesh S. Karia,
  • Jacqulyne Robichaux

摘要

Introduction

Osimertinib is recommended, alongside afatinib, as first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) with atypical mutations in the epidermal growth factor receptor gene (EGFR), a population for whom real-world data are limited. We present outcomes and subsequent treatment patterns for this population in routine US practice.

Methods

Medical records from a manually curated oncology database were analyzed for adults with stage IIIB–IV NSCLC harboring atypical EGFR mutations, treated with first-line osimertinib (April 2018–March 2020). Data were analyzed overall and by EGFR mutation subgroups: compound EGFR mutations, comprising classical (exon [Ex] 19 deletion or L858R) and atypical (G719X, L861Q, S768I, E709X, Ex19 insertions, or Ex18–25 duplications) mutations or de novo T790M only (group A), and atypical EGFR mutations only (group B). Outcomes included real-world progression-free survival (rwPFS) and overall survival (OS).

Results

A total of 55 patients were included in the study (female 76%/male 24%; group A, n = 20; group B, n = 35). After a median follow-up of 11 months, median (95% confidence interval) rwPFS and OS, respectively, were 8.8 (5.5–17.2) and 28.5 months (11.4–41.8) overall, 20.3 (10.0–44.5) and 42.5 months (27.0–not estimable) in group A, and 6.6 (4.9–24.8) and 20.0 months (9.2–32.9) in group B. At follow-up, 13% of patients (n = 7) remained on first-line osimertinib (group A, 30%; group B, 3%), 54% (n = 30) had discontinued due to death (group A, 40%; group B, 63%), and 33% (n = 18) had received subsequent treatment (group A, 30%; group B, 34%), most commonly osimertinib combinations (28%; n = 5).

Conclusions

First-line osimertinib may provide real-world clinical benefits for patients with advanced NSCLC with atypical EGFR mutations, with results suggesting greater benefit in those harboring compound EGFR mutations.