内分泌免疫相关不良事件是一个独立于领先时间偏倚的预后生物标志物。
Endocrine immune-related adverse event is a prognostic biomarker independent of lead-time bias.
机构信息
Department of Respiratory Medicine, Aomori Prefectural Central Hospital, Aomori, Japan; Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Aomori, Japan.
Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine, Aomori, Japan.
出版信息
Lung Cancer. 2024 Jun;192:107790. doi: 10.1016/j.lungcan.2024.107790. Epub 2024 Apr 9.
OBJECTIVES
Immune-related adverse events (irAEs) are known to be associated with clinical efficacy and better prognoses in patients receiving immune checkpoint inhibitors. In particular, endocrine irAE (e-irAE) is related to better prognoses. Since the incidence of irAEs increase as treatment duration becomes longer, we should consider lead-time bias not to overvalue the result. We evaluated the impact of e-irAE on the outcome before and after 6-, 9-, and 12-week landmark analyses.
MATERIALS AND METHODS
We evaluated 222 patients with advanced or recurrent non-small cell lung cancer who received anti-PD-1 antibodies such as nivolumab or pembrolizumab from January 2016 to April 2021. Treatment efficacy and outcomes of patients with or without e-irAE (e-irAE group or no e-irAE group) were retrospectively evaluated. In addition, we performed 6-, 9-, and 12-week landmark analyses to exclude the effect of lead-time bias.
RESULTS
Median progression free survival (PFS) was significantly longer in the e-irAE group than in the no e-irAE group (overall: 15.3 vs 3.9 months, p < 0.0001; 6-week: 15.3 vs 4.9 months, p < 0.0002; 9-week: 19.8 vs 6.1 months, p = 0.0012, 12-week: 19.8 vs 8.4 months, p = 0.017). Overall survival (OS) was significantly longer in the e-irAE group (overall: not reached (NR) vs 15.4 months, p = 0.0003; 6-week: NR vs 19.1 months, p = 0.0049, 9-week: NR vs 22.2 months, p = 0.006; 12-week: NR vs 23.3 months, p = 0.04). We used the multivariate cox proportional hazard model to adjust for confounding factors and found that e-irAE had better impact on both PFS and OS (PFS: overall: hazard ratio 0.37 [95% confidence interval 0.23-0.56], 6-week: 0.41 [0.26-0.63], 9-week: 0.43 [0.24-0.63], 12-week: 0.52 [0.31-0.84]; OS: overall: 0.40 [0.22-0.68], 6-week: 0.46 [0.25-0.79], 9-week: 0.47 [0.24-0.84], 12-week: 0.58 [0.29-1.08]).
CONCLUSION
The occurrence of endocrine irAE was associated with better efficacy and prognoses regardless of the lead-time bias.
目的
免疫相关不良事件（irAEs）已知与接受免疫检查点抑制剂治疗的患者的临床疗效和更好的预后相关。特别是，内分泌 irAE（e-irAE）与更好的预后相关。由于 irAEs 的发生率随着治疗时间的延长而增加，我们应该考虑到领先时间偏倚，以免过高估计结果。我们在 6 周、9 周和 12 周的里程碑分析之前和之后评估了 e-irAE 对结局的影响。
材料和方法
我们评估了 222 名接受纳武单抗或帕博利珠单抗等抗 PD-1 抗体治疗的晚期或复发性非小细胞肺癌患者，时间为 2016 年 1 月至 2021 年 4 月。回顾性评估了有或没有 e-irAE（e-irAE 组或无 e-irAE 组）的患者的治疗效果和结局。此外，我们进行了 6 周、9 周和 12 周的里程碑分析，以排除领先时间偏倚的影响。
结果
e-irAE 组的中位无进展生存期（PFS）明显长于无 e-irAE 组（总：15.3 与 3.9 个月，p<0.0001；6 周：15.3 与 4.9 个月，p<0.0002；9 周：19.8 与 6.1 个月，p=0.0012，12 周：19.8 与 8.4 个月，p=0.017）。e-irAE 组的总生存期（OS）明显长于无 e-irAE 组（总：未达到（NR）与 15.4 个月，p=0.0003；6 周：NR 与 19.1 个月，p=0.0049，9 周：NR 与 22.2 个月，p=0.006；12 周：NR 与 23.3 个月，p=0.04）。我们使用多变量 cox 比例风险模型调整混杂因素后发现，e-irAE 对 PFS 和 OS 均有更好的影响（PFS：总：风险比 0.37 [95%置信区间 0.23-0.56]，6 周：0.41 [0.26-0.63]，9 周：0.43 [0.24-0.63]，12 周：0.52 [0.31-0.84]；OS：总：0.40 [0.22-0.68]，6 周：0.46 [0.25-0.79]，9 周：0.47 [0.24-0.84]，12 周：0.58 [0.29-1.08]）。
结论
内分泌 irAE 的发生与疗效和预后的改善相关，无论是否存在领先时间偏倚。
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