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Empirical Osimertinib as a Second-Line Treatment Is a Viable Option Following First- and Second-Generation TKI
Min-Hsi Lin1,2, Kuo-An Chu1,3, Chiu-Fan Chen1
1Division of Chest Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Background And Purpose:
Patients with advanced epidermal growth factor receptor (EGFR)-mutated adenocarcinoma often receive frontline first- and second-generation EGFR tyrosine kinase inhibitor (TKI) treatments in Taiwan. However, upon progression, not all patients undergo rebiopsy for molecular testing. In some cases, tumors are located in difficult-to-access areas, and some rebiopsy specimens are inadequate for pathological and molecular assessment. Our aim is to evaluate the efficacy of the third-generation EGFR TKI, osimertinib, in tumors with unknown T790M mutation status.
Methods:
This study retrospectively collected data from patients with EGFR-mutant advanced lung adenocarcinoma who received first-line first- or second-generation EGFR TKI therapy followed by the third-generation EGFR TKI osimertinib without rebiopsy to assess T790M mutation status between January 2015 and December 2024. Efficacy and survival outcomes are presented.
Results:
A total of 160 patients with EGFR-mutated lung adenocarcinoma at clinical stages IIIB-IVB received first- or second-generation EGFR-TKI frontline therapy. After disease progression, 82 patients were treated with osimertinib as a second-line therapy with unknown T790M mutation status. Among them, 48 patients initially received afatinib as frontline treatment, while 34 patients received erlotinib. The best tumor response rate (RR) was 42.7%, with a median time on treatment (ToT) of 5.6 months (95% CI, 4.0-9.3). Swim-plot visualization highlighted a hierarchical pattern wherein longer first-line duration frequently co-occurred with longer empirical second-line duration.
Conclusion:
Osimertinib treatment is a viable option for patients who progress on frontline first- or second-generation EGFR TKI therapy without rebiopsy and have an unknown T790M mutation status. The RR of 42.7% and median ToT of 5.6 months appear consistent with historical outcomes reported for second-line platinum-based chemotherapy. Osimertinib provides an additional treatment line for patients whose tumors are difficult to access and have an unknown T790M status, making it a valuable treatment option for these patients.
Insights
Osimertinib offers a viable treatment option for advanced EGFR-mutated lung adenocarcinoma patients progressing on first- or second-generation EGFR tyrosine kinase inhibitors (TKIs) without T790M mutation testing. This study shows a 42.7% response rate, supporting its use when rebiopsy is not feasible.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Advanced EGFR-mutated lung adenocarcinoma patients often receive first- and second-generation EGFR tyrosine kinase inhibitors (TKIs).
- Rebiopsy for T790M mutation testing after progression is not always feasible due to tumor location or inadequate specimen quality.
Purpose of the Study:
- To evaluate the efficacy of third-generation EGFR TKI, osimertinib, in patients with unknown T790M mutation status after progression on prior EGFR TKI therapy.
- To assess treatment outcomes in a real-world setting where rebiopsy is not performed.
Main Methods:
- Retrospective data collection from 82 patients with EGFR-mutated advanced lung adenocarcinoma.
- Patients received first- or second-generation EGFR TKI therapy followed by osimertinib without T790M testing.
- Efficacy and survival outcomes were analyzed.
Main Results:
- The overall best tumor response rate (RR) to osimertinib was 42.7%.
- Median time on treatment (ToT) was 5.6 months.
- A trend suggested longer first-line TKI duration correlated with longer empirical second-line osimertinib duration.
Conclusions:
- Osimertinib is a viable treatment option for patients progressing on first- or second-generation EGFR TKIs when T790M mutation status is unknown.
- The observed RR and ToT are comparable to historical data for second-line platinum-based chemotherapy.
- Osimertinib provides a valuable treatment alternative for patients with difficult-to-access tumors or inadequate rebiopsy specimens.
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