Ossato Andrea, Del Bono Luna, Gasperoni Lorenzo, Inno Alessandro, Damuzzo Vera
Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padova, Italy.
Italian Society of Clinical Pharmacy and Therapeutics (SIFaCT), Turin, Italy.
J Chemother. 2024 Oct 21:1-10. doi: 10.1080/1120009X.2024.2417600.
Immune checkpoint inhibitors (ICIs) have revolutionised the treatment of metastatic NSCLC and have become standard first-line therapy both as monotherapy, for patients with PD-L1 expression ≥50%, and in combination with chemotherapy (CT), regardless of PD-L1 expression. This study used an artificial intelligence technique, the IPDfromKM method, to reconstruct individual patient data from Kaplan-Meier curves of phase III randomised clinical trial results to provide a comparative overview of different first-line chemo-immunotherapy options. Overall survival (OS) was estimated using hazard ratios and restricted mean survival time (RMST). Ten clinical trials were included in the analysis. In the squamous population, combinations of cemiplimab + CT (HR = 0.56), pembrolizumab + CT (HR = 0.67), and nivolumab + ipilimumab + CT (HR = 0.71) significantly improved OS compared with CT alone, with no difference between treatments. At longer follow-up, nivolumab + ipilimumab + CT showed longer RMST compared to pembrolizumab + CT in the PD-L1 < 1% subgroup (24.9 months vs. 22.8 months). In non-squamous NSCLC, the survival benefit of ICIs + CT was much more homogeneous, with similar results across the different options. Overall, pembrolizumab + CT showed the best results both in terms of HR (0.68, 95%CI 0.60-0.77) and RMST at long follow-up (30.4 months in the PDL-1 ≥ 1% subgroup and 24 months in the PDL-1 < 1% population). In conclusion, there are some differences between frontline options for treating metastatic NSCLC based on tumour histology and PD-L1 expression. However, further head-to-head trials and longer follow-up are needed to clarify the clinical impact of these differences.
免疫检查点抑制剂（ICIs）彻底改变了转移性非小细胞肺癌（NSCLC）的治疗方式，已成为标准的一线治疗方案，对于PD-L1表达≥50%的患者，可作为单药治疗，对于所有PD-L1表达情况的患者，也可与化疗（CT）联合使用。本研究使用人工智能技术IPDfromKM方法，从III期随机临床试验结果的Kaplan-Meier曲线重建个体患者数据，以提供不同一线化疗免疫治疗方案的比较概述。使用风险比和受限平均生存时间（RMST）估计总生存期（OS）。分析纳入了10项临床试验。在鳞状细胞癌人群中，西米普利单抗+CT（HR = 0.56）、帕博利珠单抗+CT（HR = 0.67）和纳武利尤单抗+伊匹木单抗+CT（HR = 0.71）联合治疗与单纯CT相比，显著改善了OS，各治疗组之间无差异。在更长的随访期，在PD-L1＜1%亚组中，纳武利尤单抗+伊匹木单抗+CT与帕博利珠单抗+CT相比，显示出更长的RMST（24.9个月对22.8个月）。在非鳞状NSCLC中，ICIs+CT的生存获益更为一致，不同方案的结果相似。总体而言，帕博利珠单抗+CT在HR（0.68，95%CI 0.60-0.77）和长期随访的RMST方面均显示出最佳结果（在PDL-1≥1%亚组中为30.4个月，在PDL-1＜1%人群中为24个月）。总之，基于肿瘤组织学和PD-L1表达的转移性NSCLC一线治疗方案之间存在一些差异。然而，需要进一步的头对头试验和更长时间的随访来阐明这些差异的临床影响。
