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. 2025 Mar 18;32(3):174.
doi: 10.3390/curroncol32030174.

Unraveling Survival Determinants in Patients with Advanced Non-Small-Cell Lung Cancer with EGFR Exon 20 Insertions

Kung-Yang Wang  1 , Shih-Chieh Chang  2 , Yu-Feng Wei  3   4 , Jui-Chi Hung  1 , Chung-Yu Chen  5 , Cheng-Yu Chang  1   6
Affiliations

Unraveling Survival Determinants in Patients with Advanced Non-Small-Cell Lung Cancer with EGFR Exon 20 Insertions

Kung-Yang Wang et al. Curr Oncol. .

Abstract

Background: Lung cancer is the leading cause of cancer-related death in Taiwan. It is often associated with mutations in the epidermal growth factor receptor (EGFR) gene, with common mutations accounting for approximately 85% of all EGFR-related cases. However, the remaining 15% are caused by uncommon mutations in EGFR, mainly insertions in exon 20 (about 4%). The response to EGFR tyrosine kinase inhibitors (TKIs) can vary markedly with exon 20 insertions. However, few prior large-scale studies have examined patients with these EGFR mutations.

Methods: This study combines the databases of several large hospitals in Taiwan to analyze the effects and clinical significance of rare EGFR mutations on responses to EGFR-TKIs, considering the changes in medication.

Results: This study enrolled 38 patients with non-small-cell lung cancer and EGFR exon 20 insertions. It assessed the correlations of various predictors with progression-free survival (PFS) and overall survival (OS). It showed that among those with EGFR exon 20 insertions, the median PFS was 5.15 months, and OS reached 13 months. The median PFS was 5.4 months for afatinib, 5.7 months for chemotherapy, and 4.3 months for first-generation EGFR-TKIs.

Conclusions: EGFR-TKIs may be considered as an alternative treatment option for patients with EGFR exon 20 insertions in cases where the currently recommended therapies, such as chemotherapy with or without amivantamab, are either unavailable or intolerable. The potential use of afatinib for specific patients in this context depends on the precise characteristics of their mutation and remains to be determined.

Keywords: exon 20 insertions; non-small-cell lung cancer; rare EGFR Mutations.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of Patient Selection and Mutation Screening in Stage IV NSCLC.
Figure 2
Figure 2
Progression-free survival following initial first-line treatment.
Figure 3
Figure 3
Overall survival following the initial first-line treatment.
Figure 4
Figure 4
Progression-free survival (PFS) with different systemic treatment approaches against advanced NSCLC harboring EGFR exon 20 insertions. PFS was 5.4 months (3.0–24.9) for afatinib, 5.7 months (2.1–NA) for chemotherapy (C/T), and 4.3 months (2.2–NA) for first-generation (1G) TKIs.
See this image and copyright information in PMC

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