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已发表论文
与携带 p.E746 突变的患者相比，携带 EGFR 外显子 19 缺失 p.L747 突变的晚期非小细胞肺癌患者从化疗和第一代酪氨酸激酶抑制剂中获益更多。
Authors Guan M , Shi Q, Ye W , Gu K
Received 20 April 2025
Accepted for publication 29 October 2025
Published 7 November 2025 Volume 2025:18 Pages 1227—1241
DOI https://doi.org/10.2147/OTT.S535531
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Dr John Maher
Maojing Guan,1,2 Qingming Shi,2 Wei Ye,3 Kangsheng Gu1
1Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Department of Oncology, Anhui Chest Hospital, Hefei, 230022, People’s Republic of China; 3Department of Pathology, Anhui Chest Hospital, Hefei, 230022, People’s Republic of China
Correspondence: Kangsheng Gu, Department of Oncology, the First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, People’s Republic of China, Email 13805692145@163.com
Purpose: Sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) varies among individuals harboring exon 19 deletions (19del) at different amino acid positions and EGFR 19del or deletion–insertions (19delins), and the role of chemotherapy in this context remains unknown. Therefore, we investigated how chemotherapy and the EGFR 19del subtype affect the clinical outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with first-generation TKIs.
Patients and Methods: Eighty patients at one hospital who harbored an EGFR 19del mutation were retrospectively included. Survival analyses were performed by comparing first-line treatments, EGFR 19del variants, and the coding positions at which the deletions began.
Results: Among the 80 patients, 37 and 43 received first-generation TKIs and TKIs and chemotherapy, respectively. Progression-free survival (PFS) and overall survival (OS) were comparable between the two groups. The results were the same for patients with the EGFR p.E746 mutation (n = 56) and those with the p.L747 mutation (n = 23). However, in the subgroup of patients treated with TKIs, the results favored patients with EGFR p.E746 mutations over those with p.L747 mutations, as the median PFS differed by 4 months. In the EGFR p.L747 subgroup, PFS and OS were significantly longer in patients treated with chemotherapy and TKIs than in those treated with TKIs alone. Both EGFR p.L747 and treatment with TKIs were significant risk factors for poor PFS. Eastern Cooperative Oncology Group performance status was the only significant independent risk factor for poor OS. Compared with TKIs alone, combination therapy was associated with more grade III or IV toxicity effects.
Conclusion: Additional chemotherapy did not benefit patients with p.E746 mutations but did significantly improve the PFS and OS of those with p.L747 mutations. Thus, chemotherapy + first-generation TKI combination therapy for patients with advanced NSCLC should be carefully selected.
Keywords: progression-free survival, overall survival, first-line therapy, combination therapy
1Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Department of Oncology, Anhui Chest Hospital, Hefei, 230022, People’s Republic of China; 3Department of Pathology, Anhui Chest Hospital, Hefei, 230022, People’s Republic of China
Correspondence: Kangsheng Gu, Department of Oncology, the First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, People’s Republic of China, Email 13805692145@163.com
Purpose: Sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) varies among individuals harboring exon 19 deletions (19del) at different amino acid positions and EGFR 19del or deletion–insertions (19delins), and the role of chemotherapy in this context remains unknown. Therefore, we investigated how chemotherapy and the EGFR 19del subtype affect the clinical outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with first-generation TKIs.
Patients and Methods: Eighty patients at one hospital who harbored an EGFR 19del mutation were retrospectively included. Survival analyses were performed by comparing first-line treatments, EGFR 19del variants, and the coding positions at which the deletions began.
Results: Among the 80 patients, 37 and 43 received first-generation TKIs and TKIs and chemotherapy, respectively. Progression-free survival (PFS) and overall survival (OS) were comparable between the two groups. The results were the same for patients with the EGFR p.E746 mutation (n = 56) and those with the p.L747 mutation (n = 23). However, in the subgroup of patients treated with TKIs, the results favored patients with EGFR p.E746 mutations over those with p.L747 mutations, as the median PFS differed by 4 months. In the EGFR p.L747 subgroup, PFS and OS were significantly longer in patients treated with chemotherapy and TKIs than in those treated with TKIs alone. Both EGFR p.L747 and treatment with TKIs were significant risk factors for poor PFS. Eastern Cooperative Oncology Group performance status was the only significant independent risk factor for poor OS. Compared with TKIs alone, combination therapy was associated with more grade III or IV toxicity effects.
Conclusion: Additional chemotherapy did not benefit patients with p.E746 mutations but did significantly improve the PFS and OS of those with p.L747 mutations. Thus, chemotherapy + first-generation TKI combination therapy for patients with advanced NSCLC should be carefully selected.
Keywords: progression-free survival, overall survival, first-line therapy, combination therapy