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[Precise therapy for lung cancer patients with rare sensitive mutations of epidermal growth factor receptor]
1Department of Respiratory Diseases, Chinese PLA General Hospital, Beijing 100853, China (Currently address: Department of Respiratory Diseases, 309 Hospital of PLA, Beijing 100091, China).
Abstract:
Precise medicine is an emerging clinical therapeutic concept based on genomic and genetic information of patients. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is an important component of precise therapy for lung cancer patients. EGFR mutations occur mainly in exon 18 to 21, in which exon 19 deletion and exon 21 L858R point mutation that are known as sensitive mutations account for nearly 45% and 40%, respectively. Except for the above two mutations and T790M point mutation, the rest are rare mutations, including Ins19, Ins20, E709, G719, S768, L861 and some compound mutations. Some previous retrospective studies of small sample size and case reports showed that most of EGFR exon19 (Ins), exon 21 (L861), exon 18 (G719X) and exon20 (S768I) mutations were sensitive to TKIs. And although the exon 20 insertion mutation is usually predicted to the first and second generations of EGFR-TKIs resistance, some specific types are sensitive to the third generation of EGFR-TKIs. Currently, targeted drugs for Ins20 -Ap32788 mutation has entered into clinical trials. Patients with complex mutations have similar efficacy on EGFR-TKIs in comparison with those with single sensitivity mutations. In conclusion, when patients with rare sensitive mutations received EGFR-TKIs therapy, the efficacy and progression-free survival time is similar to or slightly lower than those with classical sensitive mutations, whereas it is higher than those with wild-type EGFR. Compared with the first generation of EGFR-TKIs, second generation EGFR-TKIs may be more suitable for the treatment of lung cancer patients harboring rare sensitive EGFR mutations.
Insights
Rare epidermal growth factor receptor (EGFR) mutations in lung cancer show similar efficacy to common mutations when treated with EGFR tyrosine kinase inhibitors (TKIs). Second-generation TKIs may be more suitable for these rare mutations.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Precision medicine utilizes patient genomic data for targeted therapies.
- Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are crucial for precision therapy in lung cancer.
- EGFR mutations in exons 18-21 drive lung cancer, with specific mutations conferring sensitivity to TKIs.
Purpose of the Study:
- To evaluate the efficacy of EGFR-TKIs in lung cancer patients with rare EGFR mutations.
- To compare the effectiveness of different generations of EGFR-TKIs for rare EGFR mutations.
Main Methods:
- Review of previous retrospective studies and case reports on EGFR mutations and TKI efficacy.
- Analysis of mutation types including exon 19 insertions, exon 20 insertions, G719X, L861, and compound mutations.
- Comparison of treatment outcomes for rare mutations versus classical mutations and wild-type EGFR.
Main Results:
- Most rare EGFR mutations (e.g., exon 19 Ins, exon 21 L861, exon 18 G719X, exon 20 S768I) show sensitivity to TKIs.
- Exon 20 insertion mutations, often resistant to earlier TKIs, may respond to third-generation TKIs.
- Patients with rare sensitive mutations have comparable or slightly lower efficacy and progression-free survival than those with classical mutations, but better than wild-type EGFR.
Conclusions:
- Rare EGFR mutations can be effectively treated with EGFR-TKIs, with outcomes similar to classical mutations.
- Second-generation EGFR-TKIs appear more suitable for treating lung cancer with rare EGFR mutations.
- Further clinical trials are investigating targeted therapies for specific rare mutations like EGFR exon 20 Ins.
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