Molecular Characteristics of the Uncommon EGFR Exon 21 T854A Mutation and Response to Osimertinib in Patients With
Lihong Zhang1, Xia Yang2, Zongjuan Ming2
1Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Background:
Epidermal growth factor receptor (EGFR) T854A is an uncommon exon 21 mutation in patients with non-small cell lung cancer (NSCLC). It was first reported in samples collected after first generation EGFR tyrosine kinase inhibitor (TKI) treatment as an acquired resistant mutation to first generation EGFR-TKI. The efficacy of osimertinib, a third generation EGFR-TKI, in these patients was not clear.
Methods:
In this study, a total of 8932 NSCLC patients with NGS data were retrospectively analyzed to investigate the molecular characteristics and clinical outcomes of patients with EGFR T854A mutation.
Results:
Eight of 8932 patients (0.09%) had EGFR T854A mutation, and 5 of them (62.5%) were treatment-naïve. Interestingly, all EGFR T854A mutations were co-occurred with EGFR L858R mutation in cis. TP53 was the most common concomitant mutation and no other driver mutation was found. Five of the 8 patients received treatment of osimertinib. Four patients achieved partial response, and one had stable disease, resulting in an overall objective response rate of 80% and disease control rate of 100%. The median progression-free survival of patients who received osimertinib was 10 months. Moreover, EGFR C797S mutation was detected in 1 patient after resistant to osimertinib treatment.
Conclusion:
Presence of EGFR T854A mutation was rare in NSCLC patients and our retrospective study provides clinical evidence that osimertinib may be an effective treatment to improve survival outcomes in patients with EGFR T854A.
Insights
Epidermal growth factor receptor (EGFR) T854A mutations are rare in non-small cell lung cancer (NSCLC). Osimertinib showed promising efficacy, with an 80% objective response rate and 100% disease control rate in patients with this mutation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epidermal growth factor receptor (EGFR) T854A is an uncommon exon 21 mutation in non-small cell lung cancer (NSCLC).
- This mutation was initially identified as acquired resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs).
- The effectiveness of third-generation EGFR-TKIs, such as osimertinib, for NSCLC patients with EGFR T854A was previously unclear.
Purpose of the Study:
- To investigate the molecular characteristics of the EGFR T854A mutation in NSCLC.
- To evaluate the clinical outcomes and efficacy of osimertinib in patients with EGFR T854A NSCLC.
Main Methods:
- Retrospective analysis of 8932 NSCLC patients with next-generation sequencing (NGS) data.
- Identification and characterization of EGFR T854A mutations and co-occurring mutations.
- Evaluation of treatment response and survival outcomes in patients treated with osimertinib.
Main Results:
- EGFR T854A mutation was found in 0.09% (8/8932) of NSCLC patients, with 62.5% treatment-naïve.
- All EGFR T854A mutations occurred with EGFR L858R in cis; TP53 was the most common co-occurring mutation.
- Five patients treated with osimertinib achieved an 80% objective response rate and 100% disease control rate, with a median progression-free survival of 10 months.
Conclusions:
- EGFR T854A is a rare mutation in NSCLC.
- Osimertinib demonstrates potential as an effective treatment for NSCLC patients with EGFR T854A mutations, improving survival outcomes.
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