Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
Clin Lung Cancer. 2020 Jul;21(4):e315-e328. doi: 10.1016/j.cllc.2020.01.003. Epub 2020 Feb 4.
Previous studies have described an association between immune-related adverse events (irAEs) and better outcomes in patients administered nivolumab for advanced non-small-cell lung cancer. However, the patients in previous studies were not stratified by potential predictive factors, such as programmed cell death ligand 1 status and treatment lines. Additionally, little is known of whether the timing and type of irAEs can inform the prediction of outcomes.
We prospectively investigated the association between irAEs and outcomes in the single-center cohort that included patients administered nivolumab in the second or later line of therapy. Subsequently, we confirmed these findings in a retrospective multicenter cohort that included patients with programmed cell death ligand 1 tumor proportion score of ≥ 50% who had received first-line pembrolizumab. The primary outcome was progression-free survival (PFS).
In the prospective cohort (n = 76), the median PFS was significantly longer for the patients experiencing irAEs within 2 weeks of beginning nivolumab compared with the PFS for those who did not (median, 5.0 months [95% confidence interval (CI), 2.1-8.6 months] vs. median, 2.0 months [95% CI, 1.9-2.5 months]; P = .046). The association was stronger with earlier (within 2 weeks) than with later (within 6 weeks) irAEs. In the retrospective cohort (n = 148), the median PFS was significantly longer for the patients with early irAEs (within 3 weeks) than for those without (median, not reached [95% CI, 5.9 months to not reached] vs. median, 6.9 months [95% CI, 4.2-9.7 months]; P = .04). Rash was common and a better predictor of outcomes in both cohorts.
Our results have provided firmer evidence of the association between the occurrence of irAEs and outcomes and suggest that early irAEs (especially rash) might better predict outcomes.
先前的研究表明，免疫相关不良事件（irAEs）与接受纳武利尤单抗治疗的晚期非小细胞肺癌患者的更好结局之间存在关联。然而，以前的研究并未对程序性死亡配体 1 状态和治疗线等潜在预测因素进行分层。此外，对于 irAEs 的发生时间和类型是否可以为结局预测提供信息，人们知之甚少。
我们前瞻性地研究了 irAEs 与二线或以上纳武利尤单抗治疗的单中心队列患者结局之间的关联。随后，我们在包括程序性死亡配体 1 肿瘤比例评分≥50%且接受一线帕博利珠单抗治疗的患者的回顾性多中心队列中验证了这些发现。主要结局是无进展生存期（PFS）。
在前瞻性队列（n=76）中，与未发生 irAEs 的患者相比，在开始纳武利尤单抗后 2 周内发生 irAEs 的患者的中位 PFS 明显更长（中位，5.0 个月[95%置信区间（CI），2.1-8.6 个月] vs. 中位，2.0 个月[95%CI，1.9-2.5 个月]；P=0.046）。与较晚（6 周内）irAEs 相比，早期（2 周内）irAEs 的关联更强。在回顾性队列（n=148）中，与未发生 irAEs 的患者相比，发生早期 irAEs（3 周内）的患者的中位 PFS 明显更长（中位，未达到[95%CI，5.9 个月至未达到] vs. 中位，6.9 个月[95%CI，4.2-9.7 个月]；P=0.04）。皮疹较为常见，在两个队列中均是更好的结局预测指标。
我们的研究结果为 irAEs 的发生与结局之间的关联提供了更确凿的证据，并表明早期 irAEs（尤其是皮疹）可能更好地预测结局。
