Division of Lung Cancer and Interventional Bronchoscopy, Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
Department of Computing, Data Science Institute, Imperial College London, London, UK.
Thorac Cancer. 2018 Dec;9(12):1648-1655. doi: 10.1111/1759-7714.12875. Epub 2018 Sep 27.
VEGF plays a key role in tumor angiogenesis and immunosuppression. VEGF-blocking has proven beneficial for EGFR mutant and wild-type nonsquamous non-small cell lung cancer (nonsq-NSCLC); however, the number of cycles and treatment line yielding the optimal benefit are unknown.
We retrospectively analyzed the data of 115 patients with advanced/metastatic nonsq-NSCLC administered at least one cycle of bevacizumab. The number of bevacizumab cycles was treated as a time-dependent covariate. Predictors of overall survival (OS) were investigated.
Bevacizumab was used as first-line treatment in 47 (40.9%) patients, with a median of five cycles (range: 1-31). Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR] 4.78, 95% confidence interval [CI] 2.68-8.51; P < 0.001), wild-type EGFR (HR 2.61, 95% CI 1.45-4.70; P = 0.001), and bleeding during bevacizumab treatment (HR 3.63, 95% CI 1.77-7.45; P < 0.001) were predictive of poor OS; the number of bevacizumab cycles and first-line administration were not. In the wild-type EGFR subgroup, the number of bevacizumab cycles (≥ 5 vs. 1-4) was associated with a significant OS benefit (HR 0.28, 95% CI 0.08-0.98; P = 0.044); first-line administration also showed an OS benefit (HR 0.48, 95% CI 0.20-1.17; P = 0.105). A significant association between the number of cycles and EGFR status was identified (P = 0.046).
OS benefit is negatively affected by bleeding events in bevacizumab-treated patients. Prolonged and early introduction of bevacizumab may provide an OS benefit for patients with wild-type EGFR nonsq-NSCLC.
VEGF 在肿瘤血管生成和免疫抑制中起关键作用。VEGF 阻断已被证明对 EGFR 突变和野生型非鳞状非小细胞肺癌（非鳞状 NSCLC）有效；然而，最佳获益的周期数和治疗线尚不清楚。
我们回顾性分析了 115 例接受至少一个周期贝伐珠单抗治疗的晚期/转移性非鳞状 NSCLC 患者的数据。贝伐珠单抗的周期数作为时间依赖性协变量进行处理。研究了总生存期（OS）的预测因素。
贝伐珠单抗作为一线治疗在 47 例（40.9%）患者中使用，中位数为 5 个周期（范围：1-31）。东部合作肿瘤组表现状态≥2（危险比[HR]4.78，95%置信区间[CI]2.68-8.51；P<0.001）、野生型 EGFR（HR 2.61，95%CI 1.45-4.70；P=0.001）和贝伐珠单抗治疗期间出血（HR 3.63，95%CI 1.77-7.45；P<0.001）是 OS 不良的预测因素；贝伐珠单抗的周期数和一线治疗并非如此。在野生型 EGFR 亚组中，贝伐珠单抗的周期数（≥5 与 1-4）与显著的 OS 获益相关（HR 0.28，95%CI 0.08-0.98；P=0.044）；一线治疗也显示出 OS 获益（HR 0.48，95%CI 0.20-1.17；P=0.105）。还确定了周期数与 EGFR 状态之间的显著相关性（P=0.046）。
贝伐珠单抗治疗患者的出血事件会对 OS 获益产生负面影响。延长和早期引入贝伐珠单抗可能为野生型 EGFR 非鳞状 NSCLC 患者带来 OS 获益。
