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Low‑dose anlotinib combined with EGFR‑TKI can be used as an alternative for EGFR‑TKI‑resistant non‑small cell lung cancer in elderly patients

The current treatment options for epidermal growth factor receptor (EGFR) mutation-positive lung cancer in the elderly with tyrosine kinase inhibitor (TKI) resistance are limited. Although chemotherapy combined with vascular endothelial growth factor inhibitors significantly improves progression-fre...

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Detalles Bibliográficos
Autores principales: Chen, Yi, Jiang, Nanyuan, Liang, Xiao, Chen, Nan, Chen, Yun, Zhang, Chen, Shi, Junfeng, Guo, Renhua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10320416/
https://www.ncbi.nlm.nih.gov/pubmed/37415629
http://dx.doi.org/10.3892/ol.2023.13909
Descripción
Sumario:The current treatment options for epidermal growth factor receptor (EGFR) mutation-positive lung cancer in the elderly with tyrosine kinase inhibitor (TKI) resistance are limited. Although chemotherapy combined with vascular endothelial growth factor inhibitors significantly improves progression-free survival (PFS) in TKI-resistant patients, it often cannot be tolerated in elderly patients, leading to treatment failure. Anlotinib is a small molecule inhibitor made in China. The application of low-dose anlotinib in elderly patients with TKI-resistant lung cancer deserves further investigation. A total of 48 elderly patients with non-small cell lung cancer (NSCLC) were enrolled to evaluate the efficacy of anlotinib combined with continuous EGFR-TKI vs. anlotinib monotherapy in patients with acquired EGFR-TKI resistance. Anlotinib was administered at a dose of 6–8 mg per day, lower than the normal dose and known as a low dose, which is well tolerated in elderly patients. There were 25 cases in the combination group and 23 cases in the anlotinib monotherapy group. The primary endpoint of the present study was PFS, and the secondary endpoints were overall survival (OS), response rate and toxicity. The median PFS (mPFS) was significantly longer in the combination group than that in the anlotinib monotherapy group: 6.0 months [95% confidence interval (CI), 4.35-7.65] compared with 4.0 months (95% CI, 3.38-4.62) (P=0.002). Analysis of the subgroups showed similar trends in results. The median OS was 32 months (95% CI, 22.04-41.96) in the combination group and 28 months (95% CI, 27.13-28.87) in the anlotinib monotherapy group (P=0.217). According to stratification analysis, second-line treatment with anlotinib combined with EGFR-TKI resulted in a better mPFS than third-line treatment (7.5 vs. 3.7 months, HR=3.477; 95% CI, 1.117-10.820; P=0.031). In the combination group, patients with gradual/local progression after EGFR-TKI failure had a longer mPFS than those with dramatic progression (7.5 vs. 6.0 months, HR=5.875; 95% CI, 1.414-10.460; P=0.015). Multivariate analyses showed that continuous EGFR-TKI combined with anlotinib after EGFR-TKI resistance was associated with longer PFS (P=0.019), whereas dramatic progression (P=0.014) had a detrimental effect on follow-up treatment. Grade 2 adverse events (AEs) were reported in four patients (17.39%) in the anlotinib monotherapy group and eight patients (32.00%) in the combination group. Of these, the most common grade 2 AEs were hypertension, fatigue, diarrhea, paronychia, mucositis and transaminase elevation. There were no grade 3/4/5 AEs. In conclusion, the present study demonstrated that low-dose anlotinib combined with EGFR-TKI is superior to anlotinib alone following EGFR-TKI failure, making it the preferred regimen for elderly patients with acquired EGFR-TKI resistance.