Center for Pharmacoeconomics and Outcomes Research, China Pharmaceutical University, Nanjing, China.
Department of Public Affairs Management, School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China.
Front Immunol. 2022 Oct 26;13:948597. doi: 10.3389/fimmu.2022.948597. eCollection 2022.
Clinical evidence suggests that first-line immune checkpoint inhibitor (ICI) combination therapies can improve survival in patients with advanced non-squamous non-small cell lung cancer (nsq-NSCLC). However, the optimal strategy remains unknown without a systematic comparison of their long-term effects.
We performed a systematic review and network meta-analysis by retrieving up-to-date literature from PubMed (National Library of Medicine, Bethesda, MD, USA), Embase (Elsevier, Amsterdam, Netherlands), MEDLINE (National Library of Medicine), ClinicalTrials.gov (National Library of Medicine), and major international conference publications. Published studies and abstracts comparing first-line ICI combination therapies with other treatments for patients with advanced nsq-NSCLC were included. Restricted mean survival time (RMST) was measured over 12 months for progression-free survival (PFS) and 18 months for overall survival (OS), and the Royston-Parmar model was used to extrapolate and compare data for the long-term outcomes.
We included a total of 11 trials involving 12 therapies and 6,130 patients. Pembrolizumab plus chemotherapy exhibited the best overall survival (OS) benefit at both 18 and 60 months [RMST = 2.95, 95% confidence interval (CI) 1.96 to 3.97; life-years gained over a 5-year period = 2.18 years]. Nivolumab plus bevacizumab plus chemotherapy was found to present the best progression-free survival (PFS) benefit at 12 months (RMST 3.02, 95% CI 2.11 to 3.91), whereas atezolizumab plus bevacizumab plus chemotherapy showed the best PFS benefit at 36 months (life-years gained over 3 years = 1.22 years). Subgroup analyses showed that among patients with programmed death-ligand 1 (PD-L1) expression ≥ 50%, atezolizumab plus chemotherapy and nivolumab plus ipilimumab resulted in superior OS benefits at 18 and 60 months, respectively. Among patients with PD-L1 expression< 1%, pembrolizumab plus chemotherapy was associated with OS benefits at both 18 and 60 months. Sintilimab plus chemotherapy was associated with relatively fewer grade ≥ 3 adverse events than other ICI combination therapies.
Our results show that ICI combination therapies showed better survival benefits than chemotherapy. Pembrolizumab plus chemotherapy could provide the best OS benefits to patients with advanced nsq-NSCLC, whereas atezolizumab plus bevacizumab plus chemotherapy could bring the best PFS benefits. The optimal ICI combination therapy varies depending on PD-L1 expression level.
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=325005, identifier CRD42022325005.
临床证据表明，一线免疫检查点抑制剂（ICI）联合疗法可改善晚期非鳞状非小细胞肺癌（nsq-NSCLC）患者的生存。然而，在没有对其长期效果进行系统比较的情况下，最佳策略仍不清楚。
我们通过检索最新文献，从PubMed（美国国立卫生研究院，贝塞斯达，MD）、Embase（爱思唯尔，荷兰阿姆斯特丹）、MEDLINE（美国国立卫生研究院）、ClinicalTrials.gov（美国国立卫生研究院）和主要国际会议出版物中进行了系统评价和网络荟萃分析。纳入了比较晚期 nsq-NSCLC 患者一线 ICI 联合治疗与其他治疗的已发表研究和摘要。无进展生存期（PFS）为 12 个月，总生存期（OS）为 18 个月，分别测量限制性平均生存时间（RMST），并使用 Royston-Parmar 模型对长期结局数据进行外推和比较。
我们共纳入了 11 项试验，涉及 12 种疗法和 6130 名患者。帕博利珠单抗联合化疗在 18 个月和 60 个月时具有最佳的总体生存（OS）获益[RMST = 2.95，95%置信区间（CI）1.96 至 3.97；5 年内获得的生命年= 2.18 年]。纳武利尤单抗联合贝伐珠单抗联合化疗在 12 个月时显示出最佳的无进展生存期（PFS）获益（RMST 3.02，95%CI 2.11 至 3.91），而阿替利珠单抗联合贝伐珠单抗联合化疗在 36 个月时显示出最佳的 PFS 获益（3 年内获得的生命年= 1.22 年）。亚组分析显示，在程序性死亡配体 1（PD-L1）表达≥50%的患者中，阿替利珠单抗联合化疗和纳武利尤单抗联合伊匹单抗在 18 个月和 60 个月时分别具有更好的 OS 获益。在 PD-L1 表达<1%的患者中，帕博利珠单抗联合化疗在 18 个月和 60 个月时均与 OS 获益相关。与其他 ICI 联合治疗相比，信迪利单抗联合化疗与较少的≥3 级不良事件相关。
我们的结果表明，ICI 联合治疗比化疗具有更好的生存获益。帕博利珠单抗联合化疗可为晚期 nsq-NSCLC 患者提供最佳的 OS 获益，而阿替利珠单抗联合贝伐珠单抗联合化疗可带来最佳的 PFS 获益。最佳的 ICI 联合治疗方案取决于 PD-L1 表达水平。
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=325005，标识符 CRD42022325005。
