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Tyrosine Kinase Inhibitor Activity in Patients with NSCLC Harboring Uncommon EGFR Mutations: A Retrospective
Sanjay Popat1,2, Te-Chun Hsia3,4, Jen-Yu Hung5
1Lung Unit, Royal Marsden National Health Service Foundation Trust, London, UK.
Background:
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) are standard of care for patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) with common mutations (Del19 or L858R); however, 7%-23% of NSCLC tumors harbor uncommon EGFR mutations. These mutations are highly heterogeneous, and developments in detection techniques are helping to identify mutations with little or no clinical data.
Patients And Methods:
In this retrospective, global, multi-center study (NCT04179890), existing health records were identified for consecutive EGFR TKI-naïve patients with uncommon EGFR mutations (T790M, ex20ins, major uncommon [G719X, L861Q, or S768I], or "other" mutations; compound mutations) treated with erlotinib, gefitinib, afatinib, or osimertinib in first or second line. Endpoints included time-to-treatment failure (TTF), objective response rate (ORR), and overall survival (OS).
Results:
Overall, 246 patients (median age: 69.5 years; Asian: 84%) were included from 9 countries. Most patients (92%) received an EGFR TKI as first-line therapy; 54%, 43% and 3% received afatinib, first-generation TKIs, and osimertinib, respectively. Median TTF and OS with EGFR TKIs were 9.9 and 24.4 months; ORR was 43%. In patients treated with first-line chemotherapy (n = 20), median TTF and ORR were 6.6 months and 41%. Outcomes were most favorable in patients with major uncommon or compound mutations. Overall, TTF was 11.3 months with afatinib and 8.8 months with first-generation EGFR TKIs across mutation categories. In most mutation categories, median OS was >2 years.
Conclusion:
In a real-world setting, EGFR TKIs were the preferred treatment option in patients with uncommon EGFR mutations; strongest outcomes were seen in patients with major uncommon and compound mutations.
Insights
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) show promise for non-small cell lung cancer (NSCLC) with uncommon mutations. Real-world data indicate EGFR TKIs are preferred, with best outcomes in major uncommon and compound mutations.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Standard treatments for EGFR mutation-positive non-small cell lung cancer (NSCLC) include EGFR tyrosine kinase inhibitors (TKIs) for common mutations (Del19, L858R).
- A significant proportion of NSCLC tumors (7%-23%) harbor uncommon EGFR mutations, presenting a challenge due to their heterogeneity and limited clinical data.
- Advances in detection methods are crucial for identifying these uncommon mutations and understanding their clinical implications.
Purpose of the Study:
- To evaluate the real-world effectiveness of EGFR TKIs in patients with uncommon EGFR mutations in non-small cell lung cancer.
- To compare outcomes across different types of uncommon EGFR mutations and various EGFR TKIs.
- To assess the time-to-treatment failure (TTF), objective response rate (ORR), and overall survival (OS) in this patient population.
Main Methods:
- A retrospective, global, multi-center study (NCT04179890) identified health records of EGFR TKI-naïve patients with uncommon EGFR mutations.
- Patients received first- or second-line treatment with erlotinib, gefitinib, afatinib, or osimertinib.
- Key endpoints included TTF, ORR, and OS, with subgroup analyses based on mutation type and treatment.
Main Results:
- The study included 246 patients, with most (92%) receiving first-line EGFR TKIs (afatinib: 54%, first-generation TKIs: 43%, osimertinib: 3%).
- Median TTF and OS with EGFR TKIs were 9.9 and 24.4 months, respectively, with an ORR of 43%.
- Outcomes were most favorable in patients with major uncommon or compound mutations, showing higher TTF and OS compared to chemotherapy.
Conclusions:
- In real-world settings, EGFR TKIs are the preferred treatment for non-small cell lung cancer patients with uncommon EGFR mutations.
- Strongest treatment outcomes were observed in patients with major uncommon and compound EGFR mutations.
- EGFR TKIs demonstrate a valuable role in managing NSCLC with a spectrum of EGFR alterations beyond common mutations.
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