Efficacy and Safety of Chemotherapy Combined with Anlotinib in Advanced Epidermal Growth Factor Receptor-Mutant Non-Small Cell Lung Cancer with Primary Resistance to Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors: A Retrospective Cohort Study.

[INTRODUCTION] In this study, we aimed to evaluate the efficacy and safety of the combination therapy with chemotherapy and anlotinib in patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations who exhibit primary resistant to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs).

[METHODS] Clinical data were collected from patients with advanced NSCLC harboring EGFR mutations and exhibiting primary resistance to EGFR-TKI, who were treated with a combination of chemotherapy and anlotinib. The primary endpoints were overall response rate (ORR), progression-free survival (PFS), disease control rate, overall survival (OS), and treatment-related adverse events (AEs).

[RESULTS] A total of 34 patients with advanced NSCLC harboring EGFR mutations and exhibiting primary resistance to EGFR-TKI were enrolled. The ORR and DCR for the treatment with chemotherapy plus anlotinib were 32.35% and 64.71%, respectively. The median PFS and OS were 5 months and 9 months, respectively. Compared to patients with EGFR exon 19 deletion mutations, those with EGFR exon 21 L858R mutations derived greater benefit from the treatment (mPFS = 4.0 months vs. 5.0 months, p < 0.05; mOS = 9.0 months vs. 10.0 months, p < 0.05). The common AEs were myelosuppression, hypertension, proteinuria, and hand-foot syndrome. Most AEs were mild and well tolerated. These findings suggest that chemotherapy combined with anlotinib may be a promising strategy to overcome primary resistance to EGFR-TKIs in patients with advanced NSCLC.

[CONCLUSION] The combination of chemotherapy and anlotinib appears to be an effective and well-tolerated treatment strategy in patients with advanced NSCLC exhibiting primary resistance to EGFR-TKIs. Further studies are warranted to validate these findings and investigate long-term clinical outcomes.