Juarez-Garcia Ariadna, Sharma Ruchika, Hunger Matthias, Kayaniyil Sheena, Penrod John R, Chouaïd Christos
Bristol Myers Squibb, Uxbridge, UK.
ICON plc., Bangalore, India.
Lung Cancer. 2022 Apr;166:205-220. doi: 10.1016/j.lungcan.2022.03.008. Epub 2022 Mar 9.
Clinical trials have shown immunotherapy (IO) to be more effective than chemotherapy in pre-treated, advanced non-small cell lung cancer (NSCLC). However, there is a lack of understanding of its effectiveness in clinical practice, and among patient groups that are often underrepresented in trials. We aimed to summarize the existing real-world evidence (RWE) on the survival outcomes of IO in second- or higher line in advanced NSCLC.
We conducted a systematic review of real-world observational studies that reported overall survival (OS) estimates with IO, primarily nivolumab, pembrolizumab or atezolizumab, in adult, previously treated advanced or recurrent NSCLC patients. Meta-analysis was conducted using random-effect models to pool 1- and 2-year OS rates across studies. Additional subgroups were examined among patients treated with IO, including the elderly, those with poor performance status (PS) and those exhibiting metastasis.
In total, 66 studies were included, of which 46 (70%) included a nivolumab-specific study arm. Pooled 1-year and 2-year OS rates with nivolumab monotherapy were 45.6% (95% CI; 43.4-47.8) and 28.0% (95% CI; 24.8-31.4), respectively, compared to 43.9% (95% CI; 39.1-48.8) and 20.4% (95% CI; 14.7-27.6) in the mixed immune checkpoint inhibitors (ICI) group. OS rates with nivolumab were slightly lower in elderly compared to non-elderly populations. Poor PS was associated with worse survival rates, with a pooled one-year OS estimate of 27.1% in PS ≥ 2 vs 51.6% in PS < 2. The pooled 2-year OS rate with nivolumab in patients with and without brain metastases was 22.1% and 26.1% respectively, and this difference was significant in 36% of individual studies.
While the OS benefits of IO seen in real-world studies among pre-treated, advanced NSCLC patients are consistent with pivotal clinical trials, these tend to vary for the more vulnerable patient groups, such as patients with poor PS, which are often excluded from trials. Further research is needed to investigate findings in patients with brain and liver metastases.
临床试验表明，在经预处理的晚期非小细胞肺癌（NSCLC）中，免疫疗法（IO）比化疗更有效。然而，人们对其在临床实践中的有效性以及在试验中经常代表性不足的患者群体中的有效性缺乏了解。我们旨在总结关于晚期NSCLC二线或更高线治疗中IO生存结局的现有真实世界证据（RWE）。
我们对真实世界观察性研究进行了系统评价，这些研究报告了成年、先前接受过治疗的晚期或复发性NSCLC患者使用IO（主要是纳武利尤单抗、帕博利珠单抗或阿替利珠单抗）的总生存（OS）估计值。使用随机效应模型进行荟萃分析，以汇总各研究的1年和2年OS率。在接受IO治疗的患者中检查了其他亚组，包括老年人、体能状态（PS）差的患者和有转移的患者。
总共纳入了66项研究，其中46项（70%）包括纳武利尤单抗特异性研究组。纳武利尤单抗单药治疗的汇总1年和2年OS率分别为45.6%（95%CI：43.4 - 47.8）和28.0%（95%CI：24.8 - 31.4），而混合免疫检查点抑制剂（ICI）组分别为43.9%（95%CI：39.1 - 48.8）和20.4%（95%CI：14.7 - 27.6）。与非老年人群相比，老年人群中纳武利尤单抗的OS率略低。PS差与较差的生存率相关，PS≥2的患者汇总1年OS估计值为27.1%，而PS<2的患者为51.6%。有脑转移和无脑转移患者中纳武利尤单抗的汇总2年OS率分别为22.1%和26.1%，在36%的个体研究中这种差异具有显著性。
虽然在真实世界研究中，经预处理的晚期NSCLC患者中IO的OS获益与关键临床试验一致，但对于更脆弱的患者群体（如PS差的患者，这些患者通常被排除在试验之外），情况往往有所不同。需要进一步研究以调查脑转移和肝转移患者的研究结果。
