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Updated: Oct 19, 2025
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Afatinib treatment response in advanced lung adenocarcinomas harboring uncommon mutations
Teng Li1, Shouzheng Wang1, Jianming Ying2
1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background:
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have improved the prognosis of mutant lung cancer; however, the clinical application value of TKIs for nonclassical EGFR mutation is unclear, especially for patients with rare uncommon mutations.
Methods:
A retrospective study based on electronic medical records was conducted to collect data on the effectiveness of afatinib in patients with stage IIIB/IV lung adenocarcinoma (LUAD) bearing uncommon mutations between January 2017 and January 2021.
Results:
Forty-two patients with uncommon mutations treated with afatinib were enrolled. The objective response rate (ORR) was 50.0% (10 of 20 patients). The median time to treatment failure (TTF) was 11.7 months (95% confidence interval = 8.5-18.3 months). Of the 42 patients, the median TTF was 15.0, 11.7, and 16.6 months in patients with Gly719Xaa (G719X), Ser768Ile (S768I), and Leu861Gln (L861Q) mutations, respectively. In patients with the rare uncommon mutation, the median TTF was 10.0 months, and the ORR was 50.0%. Afatinib demonstrated clinical activity across a set type of specific rare uncommon mutations, including EGFR L747P, A767_V769dup, and L833V/H835L, with a case having a TTF of more than 1 year. Molecular profiling reports of 16 afatinib-resistant biopsy samples were available, and the secondary T790M mutation was detected in one patient with L833V/H835L mutation and one harboring S768I/L858R mutation.
Conclusions:
Our findings suggested that afatinib is effective in patients with uncommon mutations. Mechanisms of afatinib resistance vary and need further investigation.
Insights
Afatinib shows effectiveness in treating lung adenocarcinoma with uncommon epidermal growth factor receptor (EGFR) mutations. Further research is needed to understand varying mechanisms of afatinib resistance.
Area of Science:
- Oncology
- Medical Genetics
- Pharmacology
Background:
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have improved outcomes for mutant lung cancer.
- The clinical utility of TKIs for nonclassical EGFR mutations, particularly rare ones, remains unclear.
Purpose of the Study:
- To evaluate the effectiveness of afatinib in patients with lung adenocarcinoma (LUAD) harboring uncommon EGFR mutations.
- To assess treatment failure and response rates in this patient population.
Main Methods:
- A retrospective study analyzed electronic medical records of LUAD patients with uncommon mutations treated with afatinib.
- Data were collected between January 2017 and January 2021 for patients with stage IIIB/IV disease.
Main Results:
- Afatinib demonstrated clinical activity in patients with uncommon mutations, with an objective response rate (ORR) of 50.0%.
- Median time to treatment failure (TTF) was 11.7 months overall, with variations across specific mutations like G719X, S768I, and L861Q.
- Afatinib showed efficacy in rare mutations (e.g., L747P, A767_V769dup, L833V/H835L), with some achieving TTF over one year.
Conclusions:
- Afatinib is effective for treating lung adenocarcinoma with uncommon EGFR mutations.
- Mechanisms of afatinib resistance are diverse and warrant further investigation.
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