Sheng Jin, Yang Yunpeng, Ma Yuxiang, Yang Bijun, Zhang Yaxiong, Kang Shiyang, Zhou Ting, Hong Shaodong, Qin Tao, Hu Zhihuang, Fang Wenfeng, Huang Yan, Zhang Li
Department of Medical Oncology of Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
PLoS One. 2015 Jun 2;10(6):e0127306. doi: 10.1371/journal.pone.0127306. eCollection 2015.
The clinical outcomes of patients with NSCLC who progressed after first-line treatments remain poor. The purpose of this study was to assess the advantage of antiangiogenic therapy plus standard treatment versus standard treatment alone for this population of patients.
We conducted a rigorous search using electronic databases for eligible studies reporting antiangiogenic therapy combined with standard second-line chemotherapy versus standard second-line treatment for patient who progressed after front-line treatment. Pooled risk ratio and 95% confidence intervals were calculated using proper statistical method. Predefined subgroup analyses were conducted to identify the potential proper patients.
Thirteen phase II/III RCTs which involved a total of 8358 participants were included. Overall, there was significant improvement in OS (HR 0.94, 95%CI: 0.89-0.99, p=0.03), PFS (HR 0.80, 95%CI: 0.76-0.84, p<0.00001), ORR (RR 1.75, 95%CI: 1.55-1.98, p<0.00001) and DCR (RR 1.23, 95%CI: 1.18-1.28, p<0.00001) in the group with antiangiogenic therapy plus standard treatment versus the group with standard treatment alone. Subgroup analysis showed that OS benefit was presented only in patients treated with docetaxel plus antiangiogenic agents (HR 0.92, 95%CI: 0.86-0.99, p=0.02) and patients with non-squamous NSCLC (HR for OS 0.92, 95%CI: 0.86-0.99, p=0.02).
This study revealed that the addition of antiangiogenic agents to the standard treatments could provide clinical benefit to NSCLC patients who failed their first-line therapy. Furthermore, proper selection of the combined standard cytotoxic agent, as well as the patient population by tumor histology, is warranted for future studies and clinical application of antiangiogenic therapy.
一线治疗后病情进展的非小细胞肺癌(NSCLC)患者临床结局仍然较差。本研究旨在评估抗血管生成治疗联合标准治疗相对于单纯标准治疗对这类患者的优势。
我们通过电子数据库进行了严格检索,以查找符合条件的研究,这些研究报告了抗血管生成治疗联合标准二线化疗与一线治疗后病情进展患者的标准二线治疗的对比情况。使用适当的统计方法计算合并风险比和95%置信区间。进行预定义的亚组分析以确定潜在的合适患者。
纳入了13项II/III期随机对照试验,共涉及8358名参与者。总体而言,与单纯标准治疗组相比,抗血管生成治疗联合标准治疗组的总生存期(OS,风险比[HR] 0.94,95%置信区间[CI]:0.89 - 0.99,p = 0.03)、无进展生存期(PFS,HR 0.80,95%CI:0.76 - 0.84,p < 0.00001)、客观缓解率(ORR,RR 1.75,95%CI:1.55 - 1.98,p < 0.00001)和疾病控制率(DCR,RR 1.23,95%CI:1.18 - 1.28,p < 0.00001)均有显著改善。亚组分析显示,仅在接受多西他赛联合抗血管生成药物治疗的患者(HR 0.92,95%CI:0.86 - 0.99,p = 0.02)和非鳞状NSCLC患者(OS的HR为0.92,95%CI:0.86 - 0.99,p = 0.02)中观察到OS获益。
本研究表明,在标准治疗中添加抗血管生成药物可为一线治疗失败的NSCLC患者带来临床益处。此外,在抗血管生成治疗的未来研究和临床应用中,有必要合理选择联合使用的标准细胞毒性药物以及根据肿瘤组织学选择合适的患者群体。