Clinical difference between discontinuation and retreatment with nivolumab after immune-related adverse events in patients with lung cancer
Clinical difference between discontinuation and retreatment with nivolumab after immune-related adverse events in patients with lung cancer
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DOI：
10.1007/s00280-019-03926-y
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发表时间：
2019-10-01
影响因子：
3
通讯作者：
Kagamu, Hiroshi
中科院分区：
文献类型：
--
作者：
Mouri, Atsuto;Kaira, Kyoichi;Kagamu, Hiroshi
背景免疫检查点抑制剂(ICI)治疗因免疫相关不良事件(IRAE)而停用后，再用ICI治疗是否比停用ICI更有效，目前尚不清楚。为探讨非小细胞肺癌(NSCLC)复治的临床意义，对因irAEs导致停用nivolumab的非小细胞肺癌(NSCLC)患者的临床资料进行了回顾分析，并分析了停药与复治的临床差异。方法187例接受尼伏鲁单抗治疗的患者中，有49例(26%)因严重呼吸窘迫发作而停药。21例患者选择再次治疗(再治疗队列)，28例患者停止治疗(中断队列)。结果49例患者中最常见的需停药的irAEs依次为肺炎(59.2%)、肾上腺功能不全(8.2%)、肝功能不全(8.2%)、肾功能不全(8.2%)、结肠炎(6.1%)、甲状腺功能减退(4.1%)、皮疹(2.0%)。3级或4级初始irAEs的频率在再次治疗和停止治疗的队列中没有差异；然而，再次治疗的队列中肾功能障碍和结肠炎的发生率高于停止治疗的队列。再用nivolumab治疗的总有效率为15%，irAEs没有明显增加。中位总存活率和无进展存活率在再治疗和停止治疗的队列之间没有显著差异，无论先前的nivolumab的疗效如何。结论复治的疗效略高，但irAEs无明显增加，但在初次应用nivolumab后因IRAE而中断治疗的非小细胞肺癌患者，复治和停药的临床意义相似。
Background After the cessation of immune checkpoint inhibitor (ICI) therapy due to an immune-related adverse event (irAE), it remains unclear whether retreatment with ICI is more effective than its discontinuation. To explore the clinical significance of its retreatment, patients with non-small cell lung cancer (NSCLC) who had treatment interruption of nivolumab due to irAEs were identified and the clinical differences between discontinuation and retreatment with nivolumab were retrospectively reviewed. Methods 49 (26%) of 187 patients treated with nivolumab experienced the cessation of treatment due to a serious irAE. Retreatment was chosen in 21 patients (retreatment cohort), while 28 patients discontinued treatment (discontinuation cohort). Results The most common irAEs requiring treatment cessation in 49 patients included pneumonitis (59.2%), adrenal insufficiency (8.2%), liver dysfunction (8.2%) renal dysfunction (8.2%), colitis (6.1%), hypothyroidism (4.1%), and rash (2.0%). The frequency of grade 3 or 4 initial irAEs did not differ between the retreatment and discontinuation cohorts; however, the incidence of renal dysfunction and colitis was higher in the retreatment cohort than in the discontinuation cohort. Retreatment with nivolumab displayed an overall response rate of 15%, without a significant increase in irAEs. The median overall survival and progression-free survival did not differ significantly between the retreatment and discontinuation cohorts, irrespective of the efficacy of prior nivolumab. Conclusions Retreatment exhibited a slightly higher efficacy without a significant increase in irAEs; however, the clinical significance of retreatment and discontinuation was similar in NSCLC patients that led to treatment interruption due to any irAE after initial nivolumab.