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First-line Afatinib in Patients With Non-small-cell Lung Cancer With Uncommon EGFR Mutations in South Korea
Mi-Hyun Kim1, Chang Min Choi2, Sung Yong Lee3
1Department of Internal Medicine, Pusan National University School of Medicine and Βiomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea.
Background/Aim:
Non-small cell lung cancers (NSCLCs) harboring uncommon epidermal growth factor receptor (EGFR) mutations are heterogeneous and show variable prevalence and clinical responses to EGFR tyrosine kinase inhibitors. We investigated the characteristics of uncommon EGFR mutations and the clinical efficacy of afatinib in patients with NSCLC harboring uncommon EGFR mutations.
Patients And Methods:
In this multicenter, retrospective study, we analyzed patients with NSCLC with uncommon EGFR mutations in 16 South Korean institutes. Mutations were categorized according to their incidence: 1) major uncommon mutations (G719X and L861Q), 2) compound mutations, and 3) minor uncommon mutations (exon 20 insertion, S768I, and de novo T790M).
Results:
Of 703 patients with EGFR-mutant NSCLC, 64 (9.1%) had uncommon EGFR mutations. Afatinib demonstrated activity against tumors harboring major uncommon mutations [median time of treatment (TOT): 20.3 months, 95% confidence interval (CI)=15.1-25.5; overall survival (OS): 30.6 months, 95% CI=26.3-34.8] and compound mutations (median TOT: 12.3 months, 95% CI=7.7-17.0; OS: 29.1 months, 95% CI=20.4-37.7) but not against tumors harboring minor uncommon mutations (median TOT: 3.8 months, 95% CI=1.7-6.0; OS: 8.5 months, 95% CI=5.2-11.7). The S768I mutation was present in 14 patients (1.99%). The median TOT and OS were not significantly different between S768I mutations and resistant exon 20 mutations.
Conclusion:
Afatinib is effective in patients with NSCLC harboring major uncommon and compound EGFR mutations.
Insights
Afatinib shows effectiveness in non-small cell lung cancer (NSCLC) patients with major uncommon and compound epidermal growth factor receptor (EGFR) mutations. However, efficacy is limited for minor uncommon EGFR mutations, including exon 20 insertions.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) exhibits heterogeneity in uncommon epidermal growth factor receptor (EGFR) mutations.
- These mutations lead to variable responses to EGFR tyrosine kinase inhibitors.
Purpose of the Study:
- To investigate the characteristics of uncommon EGFR mutations in NSCLC.
- To evaluate the clinical efficacy of afatinib in NSCLC patients with uncommon EGFR mutations.
Main Methods:
- Multicenter, retrospective analysis of 703 EGFR-mutant NSCLC patients from 16 South Korean institutes.
- Categorization of uncommon EGFR mutations into major (G719X, L861Q), compound, and minor (exon 20 insertion, S768I, de novo T790M) types.
- Assessment of afatinib efficacy based on mutation type.
Main Results:
- Uncommon EGFR mutations were identified in 9.1% (64/703) of patients.
- Afatinib demonstrated significant activity in major uncommon (median TOT: 20.3 months, OS: 30.6 months) and compound mutations (median TOT: 12.3 months, OS: 29.1 months).
- Limited efficacy was observed for minor uncommon mutations (median TOT: 3.8 months, OS: 8.5 months), with no significant difference between S768I and exon 20 insertions.
Conclusions:
- Afatinib is an effective treatment for NSCLC patients with major uncommon and compound EGFR mutations.
- Treatment outcomes for minor uncommon EGFR mutations, including S768I and exon 20 insertions, remain poor with afatinib.