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Updated: Aug 26, 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 in a lung adenocarcinoma patient harboring a rare EGFR L747P mutation
Jisheng Li1, Liping Zhu2, Justin Stebbing3
1Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Abstract:
Classical activating alterations including exon 19 deletions and exon 21 L858R point mutations comprise the majority of epidermal growth factor receptor (EGFR) changes in non-small cell lung cancer. Patients with these exhibit excellent clinical responses to EGFR tyrosine kinase inhibitors (TKIs). However, rare alterations including point mutations, deletions, and insertions occur and are associated with poorer responses to EGFR TKIs. Herein, we report an unusual case of a patient with lung adenocarcinoma with an EGFR L747P mutation (c. 2239_2240TT>CC, p.L747P) that was initially misdiagnosed as EGFR exon 19 deletion by amplification refractory mutation system PCR, leading to gefitinib as first-line therapy. However, both the primary tumor, mediastinal lymph node, and brain metastasis progressed after 1 month. A re-examination of gene mutation status by next generation sequencing revealed an EGFR exon 19 L747P, and this case then responded to second-line chemotherapy and third-line afatinib.
Insights
A rare EGFR L747P mutation in lung adenocarcinoma was misdiagnosed, leading to ineffective gefitinib treatment. Subsequent testing revealed the correct mutation, enabling response to chemotherapy and afatinib.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) mutations, particularly exon 19 deletions and L858R, are common in non-small cell lung cancer (NSCLC).
- These classical mutations predict good response to EGFR tyrosine kinase inhibitors (TKIs).
- Rare EGFR alterations can lead to suboptimal responses to TKIs.
Observation:
- A lung adenocarcinoma case presented with an unusual EGFR L747P mutation.
- Initial testing misidentified the mutation as an EGFR exon 19 deletion, leading to first-line gefitinib treatment.
- The patient showed rapid progression of primary tumor, lymph node, and brain metastasis on gefitinib.
Findings:
- Next-generation sequencing correctly identified the EGFR exon 19 L747P mutation.
- The patient responded to second-line chemotherapy.
- The patient showed a positive response to third-line afatinib.
Implications:
- Accurate EGFR mutation testing is crucial for effective NSCLC treatment selection.
- Rare EGFR mutations may require alternative therapeutic strategies beyond standard TKIs.
- This case highlights the importance of re-evaluating molecular diagnostics when clinical response is poor.
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