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Updated: Mar 19, 2026
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Safety evaluation of afatinib in patients with a history of interstitial lung disease using data from an
Ryo Inose1, Kuniyoshi Hayashi2, Toshiyuki Sakaeda3
1Laboratory of Clinical Pharmacoepidemiology, Kyoto Pharmaceutical University, 5 Misasagi-nakauchi-cho, Yamashina-ku, Kyoto, 607-8414, Japan. inose2019@mb.kyoto-phu.ac.jp.
Introduction:
Afatinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is an effective treatment agent for lung cancer with uncommon epidermal growth factor receptor (EGFR) mutations. EGFR-TKIs should be administered with caution in patients with a history of interstitial lung disease (ILD); however, such patients are often excluded from clinical trials, and evidence on afatinib safety in this population remains limited.
Aim:
To exploratorily evaluate the safety profile of afatinib in patients with a history of ILD using an administrative claims database and investigate whether severe ILD events occur uniformly across patient backgrounds or cluster within specific patient profiles.
Method:
We analyzed data of patients who received afatinib between May 1, 2014 and November 30, 2020 from the administrative claims database provided by Medical Data Vision Co., Ltd. Severe ILD was defined using two claims-based operational definitions: (1) a broader primary definition combining ILD diagnostic codes and high-dose intravenous corticosteroid administration; (2) a stricter definition requiring intravenous methylprednisolone for sensitivity analysis. Classification and Regression Trees (CART) were used to exploratorily identify patient profiles associated with severe ILD.
Results:
Among 2,174 patients treated with afatinib, 12.3% (267/2,174) had a history of ILD. Using the primary definition, severe ILD occurred in 6.0% (16/267) of these patients, whereas 3.4% (9/267) met the stricter definition. Although CART analyses yielded different split variables and cutoff values across the two definitions, both consistently indicated that severe ILD events were concentrated within specific patient profiles rather than being uniformly distributed across the population.
Conclusion:
In patients with a history of ILD, the incidence of severe ILD following afatinib treatment was clarified. CART-derived findings should be interpreted as exploratory signals suggesting clustering of severe ILD events within particular patient profiles. However, as severe ILD was identified using claims-based operational definitions, outcome misclassification cannot be excluded despite sensitivity analyses. Further studies are warranted to validate these findings in independent real-world datasets with richer clinical detail and to support more precise stratification of severe ILD occurrence.
Insights
Afatinib treatment in lung cancer patients with a history of interstitial lung disease (ILD) showed a notable incidence of severe ILD. These severe events appear concentrated in specific patient profiles, not uniformly distributed.
Area of Science:
- Oncology
- Pulmonology
- Pharmacovigilance
Background:
- Afatinib is an effective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for lung cancer with uncommon EGFR mutations.
- Caution is advised for EGFR-TKIs in patients with interstitial lung disease (ILD) history due to limited safety data.
- Patients with ILD history are often excluded from clinical trials, necessitating real-world safety evaluations.
Purpose of the Study:
- To evaluate the safety profile of afatinib in patients with a history of ILD.
- To identify if severe ILD events cluster within specific patient profiles or occur uniformly.
Main Methods:
- Analysis of 2,174 patients treated with afatinib from a claims database (May 2014 - Nov 2020).
- Severe ILD defined using two claims-based operational definitions (primary and stricter).
- Classification and Regression Trees (CART) used to identify patient profiles associated with severe ILD.
Main Results:
- 12.3% of patients treated with afatinib had a history of ILD.
- Severe ILD occurred in 6.0% (primary definition) and 3.4% (stricter definition) of patients with ILD history.
- CART analyses indicated severe ILD events were concentrated within specific patient profiles.
Conclusions:
- The incidence of severe ILD in afatinib-treated patients with ILD history was clarified.
- CART findings suggest potential clustering of severe ILD events in particular patient profiles.
- Further studies with richer clinical data are needed to validate findings and stratify risk.
