Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with nivolumab: The Italian NSCLC expanded access program
Immune-related adverse events correlate with clinical outcomes in NSCLC patients treated with nivolumab: The Italian NSCLC expanded access program
复制标题
DOI：
10.1016/j.lungcan.2019.12.014
复制
发表时间：
2020-02-01
期刊：
影响因子：
5.3
通讯作者：
Giannarelli, Diana
中科院分区：
文献类型：
--
作者：
Baldini, Editta;Lunghi, Alice;Giannarelli, Diana
目的：二线nivolumab单一疗法的任何和严重级免疫相关不良事件（irAE）的发生率分别为31- 65%和2- 5%。虽然可能很严重甚至致命，但在缺乏适当治疗的情况下，此类事件可能是免疫系统激活的指标，并可能表明疗效。材料和方法：我们收集了1959例非小细胞肺癌（NSCLC）患者的记录在意大利扩大治疗计划中接受纳武利尤单抗治疗，我们记录了任何和严重级别的irAE的出现。我们使用考克斯的回归分析，回顾性地搜索毒性和疗效参数之间的相关性：结果：总体而言，342例（17.8%）患者发展的任何级别的irAE。我们观察到，发生任何级别irAE的患者均获得了显著更高的缓解率，（RR 27.2% vs 15.2%; p < 0.0001），疾病控制率（DCR 60.5% vs 40.2%; p < 0.0001），中位无进展生存期（mPFS 6.0个月[95% CI 4.9-7.1] vs 3.0 [95% CI：2.8-3.2]，p < 0.0001）和中位总生存期（mOS 16.7个月[95% CI：13.5-19.9] vs 9.4 [95% CI：8.4-10.4]，p < 0.00001）。在多变量分析中，irAE的发展仍然是纳武利尤单抗功效的独立指标（HR 1.44 [95%CI：1.22-1.71] p < 0.0001）。
Objectives: The incidence of any and of severe-grade immune-related adverse events (irAEs) with second-line nivolumab monotherapy is 31-65 % and 2-5 % respectively. While potentially serious and even fatal, in the absence of an appropriate therapy, such events might be indicators of the activation of the immune system and, potentially, of efficacy.Materials and Methods: We collected the records of 1959 non-small-cell lung cancer (NSCLC) patients treated with nivolumab in the Italian expanded access program, and we registered the appearance of any and of severe grade irAEs. We retrospectively searched for correlations between toxicity and efficacy parameters by using Cox's regression analysis.Results: Overall, 342 (17.8%) patients developed an irAE of any grade. We observed that patients developing irAE of any grade achieved a significantly higher response rate (RR 27.2% vs 15.2%; p < 0.0001), disease control rate (DCR 60.5% vs 40.2%; p < 0.0001), median progression-free survival (mPFS 6.0 months [95% CI 4.9-7.1] vs 3.0 [95% CI: 2.8-3.2], p < 0.0001) and median overall survival (mOS 16.7 months [95% CI: 13.5-19.9] vs 9.4 [95% CI: 8.4-10.4], p < 0.00001) compared to patients who did not. At multivariate analysis the development of an irAE remained an independent indicator of nivolumab efficacy (HR 1.44 [95% CI: 1.22-1.71] p < 0.0001).Conclusions: This report, performed in Caucasian NSCLC patients, showed that the appearance of irAEs correlated with outcome.