Xue Jianchao, Li Bowen, Wang Yadong, Huang Zhicheng, Liu Xinyu, Guo Chao, Zheng Zhibo, Liang Naixin, Le Xiuning, Li Shanqing
Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
Cancers (Basel). 2022 Oct 6;14(19):4894. doi: 10.3390/cancers14194894.
(1) Background: Several randomized controlled trials (RCTs) have been conducted in combination with Efficacy and Safety of Epidermal Growth Factor Receptor(EGFR)-Tyrosine Kinase Inhibitor (TKI) for the first-line treatment of patients with advanced non-small cell lung cancer; however, head-to-head comparisons of combination therapies are still lacking. Therefore, this study aims to compare the efficacy and safety of various combination treatments. (2) Methods: We conducted a systematic review and Bayesian network meta-analysis by searching MEDLINE, EMBASE, and COCHRANE for relevant RCTs. (3) Results: TKI combined with antiangiogenic therapy, chemotherapy, or radiation achieved a significant benefit compared with TKI alone for progression free survival (PFS). A combination with radiation yielded better benefits in PFS than any other treatment. In terms of overall survival (OS), only the combination with pemetrexed and carboplatin (HR = 0.63, 95% credible interval 0.43-0.86)/radiation (0.44, 0.23-0.83) was superior to TKI alone. All of the combination therapies may increase the incidence of ≥Grade 3 AEs, as the pooled RRs are over 1; different toxicity spectrums were revealed for individual treatments. (4) Conclusions: The TKI combination of radiation/pemetrexed and carboplatin could provide the best antitumor effects among the first generation TKI-based treatments. Considering safety, ramucirumab and bevacizumab may be the ideal additions to TKIs (systematic review registration: PROSPERO CRD42022350474).
(1) 背景：已经开展了多项随机对照试验（RCT），研究表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）联合用于晚期非小细胞肺癌患者的一线治疗；然而，联合治疗的直接比较仍然缺乏。因此，本研究旨在比较各种联合治疗的疗效和安全性。(2) 方法：我们通过检索MEDLINE、EMBASE和COCHRANE数据库以获取相关RCT，进行了系统评价和贝叶斯网络荟萃分析。(3) 结果：与单独使用TKI相比，TKI联合抗血管生成治疗、化疗或放疗在无进展生存期（PFS）方面取得了显著益处。联合放疗在PFS方面比其他任何治疗都产生了更好的效果。在总生存期（OS）方面，只有培美曲塞和卡铂联合（HR = 0.63，95%可信区间0.43 - 0.86）/放疗联合（0.44，0.23 - 0.83）优于单独使用TKI。所有联合治疗都可能增加≥3级不良事件的发生率，因为合并相对危险度超过1；各治疗显示出不同的毒性谱。(4) 结论：在基于第一代TKI的治疗中，放疗/培美曲塞和卡铂联合TKI可提供最佳抗肿瘤效果。考虑到安全性，雷莫西尤单抗和贝伐单抗可能是TKI的理想联合用药（系统评价注册号：PROSPERO CRD42022350474）。
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