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Research Article: Double-dose furmonertinib for patients with osimertinib-resistant advanced NSCLC: therapeutic efficacy and safety

Date Published: 2026-05-08

Abstract:
Epidermal growth factor receptor (EGFR) gene mutations play a key driving role in the development and progression of lung cancer. Currently, EGFR tyrosine kinase inhibitors (TKIs) serve as the standard first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, with the widespread use of these drugs, resistance has become increasingly prevalent, particularly with third-generation EGFR-TKIs, posing a significant bottleneck limiting survival benefits for patients. This real-world study aims to evaluate the efficacy and safety of double-dose furmonertinib in patients with advanced NSCLC who have developed resistance to prior osimertinib therapy, with the goal of offering practical insights for clinical decision-making. A retrospective analysis was conducted on 69 patients with advanced NSCLC resistant to osimertinib. The control group received platinum-based dual-agent chemotherapy, with progression leading to subsequent-line therapy. The observation group received either double-dose furmonertinib (160 mg/day, oral) or double-dose furmonertinib monotherapy in addition to the control group regimen. The observation group had significantly improved disease control rate (DCR) compared with the control group (71.1% vs 41.7%, p < 0.05) and prolonged median progression-free survival (mPFS) (4.97 months vs 3.20 months, p < 0.05). Univariate Cox regression analysis indicated that treatment group ( p = 0.021), central nervous system (CNS) metastasis ( p = 0.012), and Eastern Cooperative Oncology Group (ECOG) performance status ( p = 0.025) were factors influencing PFS in osimertinib-resistant advanced NSCLC patients. Multivariate analysis using the Cox proportional hazards model revealed that CNS metastasis ( p = 0.011) and ECOG score ?2 ( p = 0.038) were independent risk factors affecting the prognosis of osimertinib-resistant patients. Treatment with double-dose furmonertinib (95% CI: 0.196–0.750, p = 0.005) was an independent protective factor for prognosis in this patient group. There were no statistically significant differences between the two groups in the overall incidence of adverse events (AEs) (66.7% vs 70.8%, p > 0.05) or the incidence of Grade 3–4 AEs (15.6% vs 16.7%, p > 0.05). No Grade 5 treatment-related AEs were monitored in this study. Neither group experienced new adverse reaction symptoms, nor did any serious fatal AEs occur. In patients with osimertinib-resistant advanced NSCLC, the regimen comprising double-dose furmonertinib yielded promising efficacy, accompanied by an acceptable safety profile and overall tolerable treatment-related adverse events. In patients with osimertinib-resistant advanced NSCLC and CNS metastases, double-dose furmonertinib significantly prolongs PFS and demonstrates marked local control of CNS metastases.

Introduction:
Epidermal growth factor receptor (EGFR) gene mutations play a key driving role in the development and progression of lung cancer. Currently, EGFR tyrosine kinase inhibitors (TKIs) serve as the standard first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations. However, with the widespread use of these drugs, resistance has become increasingly prevalent, particularly with third-generation EGFR-TKIs, posing a significant bottleneck limiting survival benefits for…

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