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Sequential treatment in advanced non-small cell lung cancer harboring EGFR mutations
Ping-Chih Hsu1,2, John Wen-Cheng Chang3, Ching-Fu Chang3
1Division of Thoracic Oncology, Department of Thoracic Medicine, Chang Gung Memorial Hospital at Linkou, College of Medicine, Chang Gung University, Taoyuan City, Taiwan.
Background:
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatments for advanced EGFR-mutated non-small cell lung cancer (NSCLC) patients. Osimertinib is an effective therapy for NSCLC patients with acquired resistance due to T790M mutation after first- and second-generation EGFR-TKI treatment. This study aimed to analyze the clinical outcomes of sequential therapy following first-line EGFR-TKIs and the predictive factors of an acquired T790M mutation.
Methods:
Between January 2014 and December 2018, data from 2190 advanced NSCLC patients with common EGFR mutations (exon 19 deletion and L858R) receiving first- and second-generation EGFR-TKIs in Linkou, Kaohsiung, Chiayi and Keelung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed.
Results:
Until August 2021, among 1943 patients who experienced progressive disease, 526 underwent T790M mutation tests, and their T790M-positive rate was 53.6%. Exon 19 deletion mutation and progression-free survival (PFS) of >12 months were positively associated with secondary T790M mutation. Different first-line first- and second-generation EGFR-TKI therapies did not affect the appearance of acquired T790M mutations. The median overall survival (OS) was 58.3 [95% confidence interval (CI): 49.0-67.5] months among the patients with T790M mutation who received second-line osimertinib therapy compared with 31.0 (95% CI: 27.5-34.5) months among the patients without T790M mutation who received chemotherapy alone. The multivariate analysis showed that a poor performance status (score: >2), nonadenocarcinoma histology, stage IV cancer, liver metastasis, brain metastasis, PFS while on first-line EGFR-TKIs, and subsequent chemotherapy without third-generation EGFR-TKIs were significant independent unfavorable prognostic factors for OS.
Conclusion:
This study demonstrated the efficacy of first-line EGFR-TKIs and sequential osimertinib therapy. The results of our study suggest that T790M mutation tests are important for the use of subsequent osimertinib, which yielded favorable survival outcomes.
Insights
Sequential osimertinib therapy after first-line EGFR-TKIs significantly improves survival in non-small cell lung cancer (NSCLC) patients with T790M mutations. T790M mutation testing is crucial for guiding treatment decisions and optimizing outcomes.
Area of Science:
- Oncology
- Medical Genetics
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are standard treatments for advanced EGFR-mutated non-small cell lung cancer (NSCLC).
- Osimertinib is effective for NSCLC with acquired T790M resistance after first- and second-generation EGFR-TKI treatment.
- This study investigates clinical outcomes of sequential therapy post-first-line EGFR-TKIs and predictive factors for T790M mutation.
Purpose of the Study:
- To analyze clinical outcomes of sequential therapy following first-line EGFR-TKIs in advanced NSCLC patients.
- To identify predictive factors associated with acquired T790M mutations.
- To evaluate the efficacy of osimertinib in T790M-positive patients.
Main Methods:
- Retrospective analysis of 2190 advanced NSCLC patients with common EGFR mutations treated with first- and second-generation EGFR-TKIs (January 2014 - December 2018).
- T790M mutation testing was performed on 526 patients with progressive disease.
- Clinical outcomes, including progression-free survival (PFS) and overall survival (OS), were analyzed.
Main Results:
- The T790M-positive rate was 53.6% among tested patients.
- Exon 19 deletion and PFS >12 months were positively associated with secondary T790M mutation.
- Patients receiving second-line osimertinib for T790M mutation had a median OS of 58.3 months, versus 31.0 months for chemotherapy alone in T790M-negative patients.
Conclusions:
- First-line EGFR-TKIs followed by sequential osimertinib therapy demonstrate efficacy in advanced NSCLC.
- T790M mutation testing is essential for identifying patients who will benefit from subsequent osimertinib treatment.
- This sequential approach yields favorable survival outcomes for NSCLC patients with EGFR mutations.
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