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Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
The effectiveness of afatinib in patients with lung adenocarcinoma harboring complex epidermal growth factor receptor
Shang-Gin Wu1, Chong-Jen Yu1, James Chih-Hsin Yang2
1Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei.
Background And Aims:
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are effective against classical EGFR mutations in lung cancer. However, their effectiveness and the prognosis of lung cancer patients with complex EGFR mutations are not well delineated. Therefore, we aimed to investigate the treatment effectiveness of different EGFR TKIs in patients with complex EGFR mutations.
Patients And Methods:
From 2005 to 2020, we collected lung adenocarcinoma tissue samples for EGFR mutation analysis using direct Sanger sequencing. Patients with EGFR mutations treated with EGFR TKIs as first-line treatment were enrolled. Clinical characteristics, EGFR mutation status, treatment response, progression-free survival (PFS), and overall survival (OS) were analyzed.
Results:
Among 2675 patients with EGFR mutations, 239 (8.9%) had complex EGFR mutations, of whom 125 received EGFR TKI treatment as first-line treatment. Multivariate analysis revealed that afatinib was a more favorable factor for PFS than gefitinib [hazard ratio (HR), 2.01; 95% confidence interval (CI), 1.11-3.62] and erlotinib (HR, 2.61; 95% CI, 1.31-5.22), especially in patients with uncommon mutation patterns. Afatinib treatment as first-line treatment was also associated with longer OS compared with erlotinib (HR, 2.48; 95% CI, 1.20-5.12). Classical mutation pattern was associated with longer PFS (p = 0.001) and OS (p = 0.020). Secondary T790M was detected in 22 of 52 (42.3%) patients who had re-biopsied tissue samples after acquiring resistance to EGFR TKIs. There was no significant difference in secondary T790M formation after acquired resistance to the three EGFR TKIs (p = 0.261). Furthermore, three (5.8%) patients had small-cell lung cancer transformation.
Conclusion:
Afatinib is an effective first-line treatment for patients with lung adenocarcinoma harboring complex EGFR mutations, especially those with uncommon mutation patterns.
Insights
Afatinib shows superior efficacy in progression-free survival and overall survival for lung cancer patients with complex epidermal growth factor receptor (EGFR) mutations. This finding highlights afatinib as a preferred first-line treatment option for this patient group.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are established treatments for classical EGFR mutations in lung cancer.
- The clinical effectiveness and prognosis associated with complex EGFR mutations remain less understood.
- Investigating treatment outcomes for complex EGFR mutations is crucial for personalized lung cancer therapy.
Purpose of the Study:
- To evaluate the treatment effectiveness of various EGFR TKIs in patients with complex EGFR mutations.
- To compare the progression-free survival (PFS) and overall survival (OS) among different EGFR TKI treatments.
- To identify optimal first-line treatment strategies for lung adenocarcinoma patients with complex EGFR mutations.
Main Methods:
- Analysis of lung adenocarcinoma tissue samples for EGFR mutation status using direct Sanger sequencing (2005-2020).
- Enrollment of patients with EGFR mutations receiving first-line EGFR TKI treatment.
- Statistical analysis of clinical characteristics, mutation status, treatment response, PFS, and OS.
Main Results:
- Complex EGFR mutations were identified in 8.9% of 2675 EGFR-mutated lung cancer patients.
- Afatinib demonstrated improved PFS compared to gefitinib and erlotinib, particularly in uncommon mutation patterns.
- Afatinib treatment was associated with longer OS than erlotinib; classical mutations correlated with better PFS and OS.
Conclusions:
- Afatinib is an effective first-line treatment for lung adenocarcinoma patients with complex EGFR mutations.
- Uncommon mutation patterns within the complex EGFR group particularly benefit from afatinib therapy.
- Further research into resistance mechanisms and treatment sequencing is warranted.
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