Patients with Advanced Non-Small Cell Lung Cancer and the EGFR Exon 19 Deletion p.L747 Benefit from Chemotherapy and First-Generation Tyrosine Kinase Inhibitors Compared with Patients with p.E746.

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.