化疗免疫治疗与免疫治疗用于 PD-L1 表达≥50%或≥90%的晚期非小细胞肺癌一线治疗
Chemoimmunotherapy vs. Immunotherapy for First Line Treatment of Advanced Non-small Cell Lung Cancer With a PD-L1 Expression ≥50% or ≥90.
机构信息
Center for Real-world Effectiveness and Safety of Therapeutics (CREST), and Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA; Epidemiology and Drug Safety, IQVIA Real World Solutions, Wayne, PA.
Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA.
出版信息
Clin Lung Cancer. 2023 May;24(3):235-243. doi: 10.1016/j.cllc.2023.02.007. Epub 2023 Mar 1.
BACKGROUND
Evidence about the comparative effectiveness of chemoimmunotherapy vs. immunotherapy alone in patients with advanced non-small cell lung cancer (aNSCLC) and high PD-L1 expression (≥50%) or very high PD-L1 expression (≥90%) is limited because of the lack of head-to-head clinical trials.
OBJECTIVE
To compare survival in aNSCLC patients receiving first-line chemoimmunotherapy vs. immunotherapy in both the PD-L1 expression ≥50% or ≥90% subgroups, accounting for potential confounders that may influence physician decision-making.
METHODS
This cohort study used a nationwide electronic health record derived database to identify newly diagnosed cases of aNSCLC patients with PD-L1 expression of ≥50% who initiated first-line systemic therapy between October 2016 and October 2021. The exposure of interest was first-line therapy with chemoimmunotherapy or immunotherapy among patients with PD-L1 expression ≥50% or ≥90%. Survival was assessed using Kaplan-Meier curves and Cox regression. Propensity score-based inverse probability of weighting (IPW) was used to control for confounding. Because of nonproportionality of hazards, we estimated hazard ratios over the first 6 months and after 6 months for the overall cohort, and over the first 12 months and after 12 months for a subgroup of persons with a PD-L1 expression ≥90%.
RESULTS
We identified 3086 subjects who met inclusion criteria, of whom 32% received chemoimmunotherapy and 68% received immunotherapy alone. Chemoimmunotherapy was associated with no survival advantage vs. immunotherapy alone during the entire follow-up period (IPW-adjusted Hazard Ratio [aHR] 0.98, 95% CI, 0.86-1.12), but was associated with a survival benefit during the first 6 months (aHR 0.74, 95% CI, 0.61-0.90). Similarly, in the subgroup of patients with a PD-L1 expression ≥90%, chemoimmunotherapy was associated with no overall survival advantage during the entire follow-up period (aHR 0.99, 95% CI, 0.87-1.22), but was associated with a survival benefit during the first 12 months (aHR 0.74, 95% CI, 0.57-0.97).
CONCLUSION
Chemoimmunotherapy was not associated with an overall benefit over immunotherapy alone, although was associated with an early survival advantage in both the overall cohort and the subgroup of patients with a PD-L1 expression ≥90%. Future studies should focus on identifying the characteristics of higher risk patients that may benefit from the addition of chemotherapy.
背景
由于缺乏头对头的临床试验，关于在 PD-L1 表达≥50%或非常高 PD-L1 表达（≥90%）的晚期非小细胞肺癌（aNSCLC）患者中，化疗免疫治疗与单纯免疫治疗相比的比较疗效的证据有限。
目的
在 PD-L1 表达≥50%或≥90%亚组中，比较接受一线化疗免疫治疗与免疫治疗的 aNSCLC 患者的生存情况，同时考虑可能影响医生决策的潜在混杂因素。
方法
这项队列研究使用全国性的电子健康记录衍生数据库，确定了 2016 年 10 月至 2021 年 10 月期间 PD-L1 表达≥50%的新诊断为 aNSCLC 患者的一线系统治疗开始的病例。感兴趣的暴露是 PD-L1 表达≥50%或≥90%的患者的一线化疗免疫治疗或免疫治疗。使用 Kaplan-Meier 曲线和 Cox 回归评估生存情况。基于倾向评分的逆概率加权（IPW）用于控制混杂。由于危害不成比例，我们在整个队列中估计了前 6 个月和 6 个月后的危险比，以及 PD-L1 表达≥90%的亚组中前 12 个月和 12 个月后的危险比。
结果
我们确定了 3086 名符合纳入标准的患者，其中 32%接受了化疗免疫治疗，68%接受了单纯免疫治疗。与单独免疫治疗相比，化疗免疫治疗在整个随访期间没有生存优势（IPW 调整后的危险比[aHR]0.98，95%CI，0.86-1.12），但在头 6 个月有生存获益（aHR 0.74，95%CI，0.61-0.90）。同样，在 PD-L1 表达≥90%的患者亚组中，化疗免疫治疗在整个随访期间没有总体生存优势（aHR 0.99，95%CI，0.87-1.22），但在头 12 个月有生存获益（aHR 0.74，95%CI，0.57-0.97）。
结论
化疗免疫治疗与单独免疫治疗相比没有整体获益，但在整个队列和 PD-L1 表达≥90%的亚组中与早期生存优势相关。未来的研究应集中于确定可能受益于化疗的高危患者的特征。
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