Abstract
Comparison of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) monotherapy or with bevacizumab in real-world non-small cell lung cancer (NSCLC) patients was lacking. 310 patients of advanced NSCLC with common EGFR mutation receiving first-generation EGFR-TKI monotherapy or with bevacizumab were included and propensity-score matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutation were analysed. Patients receiving EGFR-TKI and bevacizumab were significantly younger, had better performance status and with high incidence of brain metastasis (55.8%). In the propensity-score matched cohort, PFS (13.5 vs. 13.7 months; log-rank p = 0.700) was similar between the two groups. The OS (61.3 vs. 34.2 months; log-rank p = 0.010) and risk reduction of death (HR 0.42 [95% CI 0.20–0.85]; p = 0.017) were significantly improved in EGFR-TKI plus bevacizumab group. Analysis of treatment by brain metastasis status demonstrated EGFR-TKI plus bevacizumab in patients with brain metastasis was associated with significant OS benefit compared to other groups (log-rank p = 0.030) and these patients had lower early-CNS and early-systemic progressions. The secondary T790M did not significantly differ between EGFR-TKI plus bevacizumab and EGFR-TKI monotherapy groups (66.7% vs. 75.0%, p = 0.460). Forty-one (31.1%) and 31 (23.5%) patients received subsequent osimertinib and chemotherapy, respectively. The post-progression OS of osimertinib and chemotherapy were 22.1 and 44.9 months in EGFR-TKI plus bevacizumab group and were 10.0 and 14.1 months in EGFR-TKI monotherpay group, respectively. First-generation EGFR-TKI with bevacizumab improved treatment efficacy in real-world patients of NSCLC with EGFR mutation. Patients with brain metastasis received additional OS benefit from this treatment.
Highlights
Erlotinib and gefitinib are first-generation EGFR-TKIs with non-covalent and reversible binding activity to receptor tyrosine kinase and are both approved treatments for patients of advanced non-small cell lung cancer (NSCLC) harboring sensitizing EGFR mutation[1,2]
310 patients were included in present study in which 267 (86.1%) patients received the treatment of single-agent EGFR-TKI and 43 (13.9%) patients received the treatment of EGFR-TKI plus bevacizumab
The present study demonstrated a superior overall survival (OS) of first-generation EGFR-TKI plus bevacizumab compared to first-generation EGFR-TKI monotherapy in a real-world cohort of EGFR-mutant NSCLC patients with sensitizing mutation
Summary
Erlotinib and gefitinib are first-generation EGFR-TKIs with non-covalent and reversible binding activity to receptor tyrosine kinase and are both approved treatments for patients of advanced NSCLC harboring sensitizing EGFR mutation[1,2]. A number of combination strategies were attempted in the hope to improve the treatment efficacy of singleagent EGFR-TKI. This includes anti-angiogenesis agents that target vascular endothelial growth factor (VEGF) or VEGF receptor 2 (VEGFR2)[7]. Demonstrated PFS benefit of erlotinib plus bevacizumab compared to erlotinib monotherapy in the front-line treatment of advanced NSCLC with sensitizing EGFR mutation[9,10]. Stinchcombe et al conducted a phase II randomized study comparing erlotinib monotherapy and with bevacizumab in a Caucasian cohort of EGFR-mutant NSCLC p atients[11]. Significantly improved OS of bevacizumab treatment in advanced NSCLC patients with brain metastasis compared to those without was observed in a real-world US cancer registry and claim d atabase[15]. The survival benefit of bevacizumab treatment in EGFR-mutant NSCLC patients with brain metastasis warrants further investigation
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