Department of Respiratory Disease, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Medicine (Baltimore). 2021 Feb 5;100(5):e23712. doi: 10.1097/MD.0000000000023712.
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) significantly improve outcomes of patients with EGFR-mutated non-small-cell lung cancer (NSCLC). However, acquired resistance inevitably emerges and remains a major challenge. The present study aimed to evaluate the efficacy of EGFR-TKIs plus bevacizumab in advanced non-squamous NSCLC patients with gradual progression on EGFR-TKIs.Advanced non-squamous EGFR-mutated NSCLC patients with gradual progression on EGFR-TKIs were administered bevacizumab while EGFR-TKIs were continued until disease progression occurred. Tumor lesions were assessed, and blood samples were collected at the start of the combination treatment and every 6 weeks until disease progression.Among the 15 included patients, there were no grade 3 or higher adverse events (AEs). Partial response (PR) and stable disease (SD) were achieved in 1 and 13 patients, respectively, with an objective response rate (ORR) of 6.7% and a disease control rate (DCR) of 93.3%. The median progression-free survival 2 (PFS2), defined as the time from the initiation of combination treatment to disease progression, was 5.0 (95% confidence interval [CI]: 4.0-6.0) months. Additionally, Spearman correlation analysis revealed that PFS2 was positively correlated with the serum vascular endothelial growth factor (VEGF) level at baseline (r = 0.7212, P = .0234). Patients with high baseline serum VEGF levels showed a better median PFS2 than those with low baseline serum VEGF levels (5.5 months vs 3.6 months, P = .0333).EGFR-TKIs plus bevacizumab led to a durable prolongation of PFS in non-squamous NSCLC patients with gradual progression on EGFR-TKIs. This therapeutic regimen was well tolerated and could be a promising strategy for these patients. Serum VEGF could be a potential biomarker to predict a subset of patients who are likely to benefit from EGFR-TKIs combined with bevacizumab.
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）显著改善了 EGFR 突变型非小细胞肺癌（NSCLC）患者的预后。然而，获得性耐药不可避免地出现，仍然是一个主要挑战。本研究旨在评估 EGFR-TKIs 联合贝伐珠单抗在 EGFR-TKIs 逐渐进展的晚期非鳞状 NSCLC 患者中的疗效。
在 EGFR-TKIs 逐渐进展的晚期非鳞状 EGFR 突变型 NSCLC 患者中，在继续使用 EGFR-TKIs 的同时给予贝伐珠单抗，直到疾病进展。在联合治疗开始时和每 6 周采集肿瘤病变的评估和血液样本，直到疾病进展。
在 15 名纳入的患者中，没有发生 3 级或更高级别的不良事件（AE）。1 名患者达到部分缓解（PR），13 名患者达到稳定疾病（SD），客观缓解率（ORR）为 6.7%，疾病控制率（DCR）为 93.3%。无进展生存期 2（PFS2）的中位数定义为从联合治疗开始到疾病进展的时间，为 5.0（95%置信区间[CI]：4.0-6.0）个月。此外，Spearman 相关分析显示，PFS2 与基线时血清血管内皮生长因子（VEGF）水平呈正相关（r=0.7212，P=0.0234）。基线时血清 VEGF 水平较高的患者中位 PFS2 优于基线时血清 VEGF 水平较低的患者（5.5 个月比 3.6 个月，P=0.0333）。
EGFR-TKIs 联合贝伐珠单抗可延长 EGFR-TKIs 逐渐进展的非鳞状 NSCLC 患者的无进展生存期。这种治疗方案耐受性良好，可能是这些患者的一种有前途的策略。血清 VEGF 可能是预测可能从 EGFR-TKIs 联合贝伐珠单抗中获益的患者亚群的潜在生物标志物。
