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Objective <p>To compare treatment outcomes between first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) in patients with EGFR co-mutated non-small cell lung cancer (NSCLC).</p> Background <p>EGFR mutation is one of the most common genetic alterations in NSCLC; however, the management of patients harboring EGFR co-mutations has emerged as a major therapeutic challenge in recent years.</p> Materials and methods <p>We conducted a retrospective cohort study (2018–2025) at Vietnam National Lung Hospital analyzing 81 treatment-naïve advanced NSCLC patients with EGFR co-mutations identified by next-generation sequencing. Patients received first- or second-generation EGFR-TKIs, with efficacy evaluated using RECIST v1.1 criteria.</p> Results <p>Among 81 patients with EGFR co-mutations, dual EGFR mutations were the most common (43%), followed by EGFR combined with PIK3CA (20%), ALK (14%), and KRAS (9%). Multivariate analysis suggested patients with EGFR dual mutations were correlated with higher overall survival (OS) compared with other co-mutation patterns (HR 0.26, 95% CI 0.09–0.76, <i>p</i> = 0.01). No significant differences were observed between first- and second-generation EGFR TKIs in objective response rate (56.5% vs. 73.5%, <i>p</i> = 0.181) or disease control rate, with both achieving a median progression-free survival (PFS) of 9 months. Subgroup analyses showed significantly longer OS with first-generation TKIs in female patients (27.59 vs. 22.72 months, <i>p</i> = 0.003) and brain metastatic groups (27.59 vs. 10.43 months, <i>p</i> = 0.032), whereas PFS remained comparable (9.10 vs. 7.23 months, <i>p</i> = 0.103).</p> Conclusion <p>First- and second-generation EGFR-TKIs demonstrated comparable overall treatment outcomes in NSCLC patients harboring EGFR co-mutations. However, subgroup analyses suggested potential differences in clinical benefit among female patients and those with brain metastases, warranting further investigation.</p>

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Real-world efficacy of first- and second-generation EGFR TKIs in NSCLC with EGFR co-mutations: a Vietnamese cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月12日

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  • Luong Van Dinh,
  • Ngoc Bích Thi Nguyen,
  • Trung Quoc Vu,
  • Hieu Huy Dang,
  • Trang Doan Nguyen,
  • Linh Tu Le

摘要

Objective

To compare treatment outcomes between first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) in patients with EGFR co-mutated non-small cell lung cancer (NSCLC).

Background

EGFR mutation is one of the most common genetic alterations in NSCLC; however, the management of patients harboring EGFR co-mutations has emerged as a major therapeutic challenge in recent years.

Materials and methods

We conducted a retrospective cohort study (2018–2025) at Vietnam National Lung Hospital analyzing 81 treatment-naïve advanced NSCLC patients with EGFR co-mutations identified by next-generation sequencing. Patients received first- or second-generation EGFR-TKIs, with efficacy evaluated using RECIST v1.1 criteria.

Results

Among 81 patients with EGFR co-mutations, dual EGFR mutations were the most common (43%), followed by EGFR combined with PIK3CA (20%), ALK (14%), and KRAS (9%). Multivariate analysis suggested patients with EGFR dual mutations were correlated with higher overall survival (OS) compared with other co-mutation patterns (HR 0.26, 95% CI 0.09–0.76, p = 0.01). No significant differences were observed between first- and second-generation EGFR TKIs in objective response rate (56.5% vs. 73.5%, p = 0.181) or disease control rate, with both achieving a median progression-free survival (PFS) of 9 months. Subgroup analyses showed significantly longer OS with first-generation TKIs in female patients (27.59 vs. 22.72 months, p = 0.003) and brain metastatic groups (27.59 vs. 10.43 months, p = 0.032), whereas PFS remained comparable (9.10 vs. 7.23 months, p = 0.103).

Conclusion

First- and second-generation EGFR-TKIs demonstrated comparable overall treatment outcomes in NSCLC patients harboring EGFR co-mutations. However, subgroup analyses suggested potential differences in clinical benefit among female patients and those with brain metastases, warranting further investigation.