Zhao Yongzhao, Wang Huixian, Shi Yan, Cai Shangli, Wu Tongwei, Yan Guangyue, Cheng Sijin, Cui Kang, Xi Ying, Qi Xiaolong, Zhang Jie, Ma Wang
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
School of Medicine, Tongji University, Shanghai, China.
Oncotarget. 2017 Jan 24;8(4):7014-7024. doi: 10.18632/oncotarget.12294.
BACKGROUND & AIMS: Combined therapy inhibiting EGFR and VEGF pathways is becoming a promising therapy in the treatment of advanced non-small-cell lung cancer (NSCLC), however, with controversy. The study aims to compare the efficacy of combined inhibition therapy versus control therapy (including placebo, single EGFR inhibition and single VEGF inhibition) in patients with advanced NSCLC.
An adequate literature search in EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) was conducted. Phase II or III randomized controlled trials (RCTs) that compared effectiveness between combined inhibition therapy and control therapy in patients with advanced NSCLC were eligible. The endpoint was overall response rate (ORR), progression free survival (PFS) and overall survival (OS).
Sixteen phase II or III RCTs involving a total of 7,109 patients were included. The results indicated that the combined inhibition therapy significantly increased the ORR (OR = 1.59, 95% CI = 1.36-1.87, p<0.00001; I2 = 36%) when compared to control therapy. In the subgroup analysis, the combined inhibition therapy clearly increased the ORR (OR = 2.04, 95% CI = 1.60-2.60, p<0.00001; I2 = 0%) and improved the PFS (HR = 0.78, 95% CI = 0.71-0.85, p<0.00001;I2 = 0%) when compared with the placebo, and similar results was detected when compared with the single EGFR inhibition in terms of ORR (OR = 1.39, 95% CI = 1.12-1.74, p = 0.003; I2 = 30%) and PFS (HR = 0.73, 95% CI = 0.67-0.81, p<0.0001; I2 = 50%). No obvious difference was found between the combined inhibition therapy and single VEGF inhibition in term of ORR, however, combined inhibition therapy significantly decreased the PFS when compared to the single VEGF inhibition therapy (HR = 1.70, 95% CI = 1.34-2.17, p<0.0001; I2 = 50%). Besides, no significant difference was observed between the combined inhibition therapy and control therapy in term of OS (including placebo, single EGFR inhibition and single VEGF inhibition) (HR = 0.98, 95% CI = 0.92-1.04, p = 0.41; I2 = 0%).
Combined inhibition therapy was superior to placebo and single EGFR inhibition in terms of ORR, PFS for advanced NSCLC, however, no statistical difference were found in term of OS. Besides, combined inhibition therapy was not superior to single VEGF inhibition in terms of ORR, PFS and OS. Therefore, combined inhibition therapy is recommended to treat advanced NSCLC patients.
抑制表皮生长因子受体（EGFR）和血管内皮生长因子（VEGF）通路的联合治疗正成为晚期非小细胞肺癌（NSCLC）治疗中一种有前景的疗法，但仍存在争议。本研究旨在比较联合抑制疗法与对照疗法（包括安慰剂、单一EGFR抑制和单一VEGF抑制）在晚期NSCLC患者中的疗效。
在EMBASE、Cochrane对照试验中心注册库（CENTRAL）、美国临床肿瘤学会（ASCO）和欧洲医学肿瘤学会（ESMO）进行了充分的文献检索。比较联合抑制疗法与对照疗法在晚期NSCLC患者中有效性的II期或III期随机对照试验（RCT）符合要求。终点指标为总缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。
纳入了16项II期或III期RCT，共涉及7109例患者。结果表明，与对照疗法相比，联合抑制疗法显著提高了ORR（OR = 1.59，95%CI = 1.36 - 1.87，p<0.00001；I2 = 36%）。在亚组分析中，与安慰剂相比，联合抑制疗法明显提高了ORR（OR = 2.04，95%CI = 1.60 - 2.60，p<0.00001；I2 = 0%）并改善了PFS（HR = 0.78，95%CI = 0.71 - 0.85，p<0.00001；I2 = 0%），与单一EGFR抑制相比，在ORR（OR = 1.39，95%CI = 1.12 - 1.74，p = 0.003；I2 = 30%）和PFS（HR = 0.73，95%CI = 0.67 - 0.81，p<0.0001；I2 = 50%）方面也检测到类似结果。在ORR方面，联合抑制疗法与单一VEGF抑制之间未发现明显差异，然而，与单一VEGF抑制疗法相比，联合抑制疗法显著降低了PFS（HR = 1.70，95%CI = 1.34 - 2.17，p<0.0001；I2 = 50%）。此外，在OS方面（包括安慰剂、单一EGFR抑制和单一VEGF抑制），联合抑制疗法与对照疗法之间未观察到显著差异（HR = 0.98，95%CI = 0.92 - 1.04，p = 0.41；I2 = 0%）。
在晚期NSCLC的ORR、PFS方面，联合抑制疗法优于安慰剂和单一EGFR抑制，但在OS方面未发现统计学差异。此外，在ORR、PFS和OS方面，联合抑制疗法并不优于单一VEGF抑制。因此，推荐联合抑制疗法用于治疗晚期NSCLC患者。
