Peng Ling, Liang Wen-Hua, Mu De-Guang, Xu Song, Hong Shao-Dong, Stebbing Justin, Liang Fei, Xia Yang
Department of Respiratory Disease, Zhejiang Provincial People's Hospital, Hangzhou, China.
National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Front Oncol. 2021 Jun 23;11:657545. doi: 10.3389/fonc.2021.657545. eCollection 2021.
First-line treatment strategies for programmed death-ligand 1 (PD-L1) negative non-small cell lung cancer (NSCLC) patients include chemotherapy and combination with anti-angiogenesis drugs and/or immune checkpoint inhibitor. We conducted a Bayesian network meta-analysis to evaluate the efficacy of these therapeutic options.
We included phase III randomized controlled trials comparing two or more treatments in the first-line setting for NSCLC, including data in PD-L1-negative patients. First-line strategies were compared and ranked based on the effectiveness in terms of overall survival (OS) and progression-free survival (PFS). A rank was assigned to each treatment after Markov Chain Monte Carlo analyses.
Fourteen trials involving 14 regimens matched our eligibility criteria. For OS, none of the treatment were significantly more effective than chemotherapy. Nivolumab plus ipilimumab plus chemotherapy was probably the best option based on analysis of the treatment ranking (probability = 30.1%). For PFS, nivolumab plus chemotherapy plus bevacizumab, atezolizumab plus chemotherapy plus bevacizumab, and atezolizumab plus chemotherapy were statistically superior to chemotherapy in pairwise comparison. Nivolumab plus chemotherapy plus bevacizumab was likely to be the preferred option based on the analysis of the treatment ranking (probability = 72.9%).
Nivolumab plus chemotherapy, in combination with angiogenesis inhibition or anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), had maximal benefits for NSCLC patient of PD-L1-negative expression. These findings may facilitate individualized treatment strategies. Safety at an individual patient level should be considered in decision making. Further validation is warranted.
程序性死亡配体1（PD-L1）阴性的非小细胞肺癌（NSCLC）患者的一线治疗策略包括化疗以及联合抗血管生成药物和/或免疫检查点抑制剂。我们进行了一项贝叶斯网络荟萃分析，以评估这些治疗方案的疗效。
我们纳入了在NSCLC一线治疗中比较两种或更多种治疗方法的III期随机对照试验，包括PD-L1阴性患者的数据。根据总生存期（OS）和无进展生存期（PFS）的有效性对一线治疗策略进行比较和排序。在马尔可夫链蒙特卡罗分析后为每种治疗方法赋予一个排名。
14项涉及14种治疗方案的试验符合我们的纳入标准。对于OS，没有一种治疗方法比化疗显著更有效。基于治疗排名分析，纳武利尤单抗加伊匹木单抗加化疗可能是最佳选择（概率 = 30.1%）。对于PFS，纳武利尤单抗加化疗加贝伐单抗、阿替利珠单抗加化疗加贝伐单抗以及阿替利珠单抗加化疗在两两比较中在统计学上优于化疗。基于治疗排名分析，纳武利尤单抗加化疗加贝伐单抗可能是首选方案（概率 = 72.9%）。
纳武利尤单抗加化疗，联合血管生成抑制或抗细胞毒性T淋巴细胞相关抗原4（CTLA-4），对PD-L1阴性表达的NSCLC患者具有最大益处。这些发现可能有助于制定个体化治疗策略。在决策时应考虑个体患者层面的安全性。有必要进行进一步验证。
