Uncommon EGFR mutations in non-small-cell lung cancer: A systematic literature review of prevalence and clinical outcomes
- Author(s)
- John, T; Taylor, A; Wang, H; Eichinger, C; Freeman, C; Ahn, MJ;
- Journal Title
- Cancer Epidemiology
- Publication Type
- Review
- Abstract
- Mutations in exons 18-21 of the epidermal growth factor receptor gene (EGFR) can confer sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) in patients with non-small-cell lung cancer (NSCLC). Deletions in exon 19 or the exon 21 L858R substitution comprise approximately 85% of mutations, but comparatively few data are available on the remaining "uncommon" mutations. We conducted a systematic literature review to identify evidence on uncommon EGFR mutations in locally advanced/metastatic NSCLC (PROSPERO registration number: CRD42019126583). Electronic screening and congress searches identified studies published in 2012-2020 including patients with locally advanced/metastatic NSCLC and uncommon EGFR mutations (excluding T790M). We assessed the prevalence of uncommon mutations (in studies using direct sequencing of exons 18-21), and compared response to treatment and progression-free survival (PFS) in patients with common versus uncommon mutations and in those with exon 20 mutations versus other uncommon mutations. We identified 64 relevant studies. Uncommon mutations constituted 1.0-18.2% of all EGFR mutations, across 10 studies. The most frequently reported uncommon mutations were G719X (0.9-4.8% of all EGFR mutations), exon 20 insertions (Ex20ins; 0.8-4.2%), L861X (0.5-3.5%), and S768I (0.5-2.5%). Patients with common mutations typically experienced better treatment response and longer PFS on EGFR-TKIs than patients with uncommon mutations; Ex20ins mutations were associated with less favourable outcomes than other uncommon mutations. This review shows that uncommon mutations may comprise a clinically significant proportion of the EGFR mutations occurring in NSCLC, and highlights disparities in EGFR-TKI sensitivity between different uncommon mutations.
- Keywords
- *Carcinoma, Non-Small-Cell Lung/drug therapy/epidemiology/genetics; ErbB Receptors/genetics; Humans; *Lung Neoplasms/drug therapy/epidemiology/genetics; Mutation; Prevalence; Protein Kinase Inhibitors/therapeutic use; Carcinoma; EGFR gene; Exon; Non-small-cell lung; Progression-free survival
- Department(s)
- Medical Oncology
- PubMed ID
- 34922050
- Publisher's Version
- https://doi.org/10.1016/j.canep.2021.102080
- Open Access at Publisher's Site
https://doi.org/10.1016/j.canep.2021.102080- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2024-12-19 03:18:22
Last Modified: 2024-12-19 03:23:08