Efficacy and safety of nivolumab in previously treated patients with non-small cell lung cancer: A multicenter retrospective cohort study
Efficacy and safety of nivolumab in previously treated patients with non-small cell lung cancer: A multicenter retrospective cohort study
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DOI：
10.1016/j.lungcan.2018.02.017
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发表时间：
2018-05-01
期刊：
影响因子：
5.3
通讯作者：
Hirai, Toyohiro
中科院分区：
文献类型：
--
作者：
Fujimoto, Daichi;Yoshioka, Hiroshige;Hirai, Toyohiro
Nivolumab已被证明对先前治疗过的晚期非小细胞肺癌（NSCLC）患者有效且安全。然而，人们对其在真实世界（即非试验）环境中的表现知之甚少。此外，对于不符合临床试验资格或在此类试验中被分类为小亚组的患者，nivolumab的疗效尚不清楚。方法：我们对2016年1月至12月接受纳武单抗单药治疗的晚期NSCLC患者进行了一项15个中心的观察性、回顾性队列研究。结果：本研究纳入的613例患者中，141例表现不佳，106例EGFR突变或ALK重排阳性。有效率和疾病控制率分别为20%和44%；估计1年无进展生存期（PFS）为18%。多变量分析发现从不吸烟、不良PS和EGFR突变/ALK重排是PFS的独立阴性预测因子。最常见的>= 3级不良事件是肺炎（5%的患者）。重度肺炎（>= 3级）发生时间明显早于轻度肺炎（1.6个月vs 2.3个月，P = 0.031）。肺炎患者比无肺炎患者获得更高的缓解率和更长的PFS（分别为37%对18%，5.8对2.1个月；P = 0.002）。结论：吸烟状况、PS和EGFR突变/ALK重排是PFS的独立预测因素。我们的研究阐明了nivolumab在以前被低估的患者群体中的疗效；即，那些PS差和/或有驱动癌基因的人。我们还发现肺炎并不罕见，并对结果有关键影响。这些数据应该有助于改善尼伏单抗治疗的非小细胞肺癌患者的临床病程。
Introduction: Nivolumab has been shown to be effective and safe in previously treated patients with advanced non-small cell lung cancer (NSCLC). However, little is known regarding its performance in real-world (i.e., non-trial) settings. Furthermore, nivolumab efficacy is unknown in patients who are ineligible for clinical trials or who are categorized into small subgroups in such trials.Methods: We conducted a 15-center, observational, retrospective cohort study of patients with advanced NSCLC who received nivolumab monotherapy between January and December 2016.Results: Of 613 patients included in our study, 141 had poor performance status (PS) and 106 were EGFR mutation or ALK rearrangement-positive. The response and disease control rates were 20% and 44%, respectively; the estimated 1-year progression-free survival (PFS) was 18%. Multivariate analysis identified never smoking, poor PS, and EGFR mutation/ALK rearrangement as independent negative predictors of PFS. The most frequently reported grade >= 3 adverse event was pneumonitis (5% of patients). Severe pneumonitis (grade >= 3) occurred significantly earlier than mild pneumonitis (1.6 vs. 2.3 months, P = 0.031). Patients with pneumonitis achieved higher response rates and longer PFS than those without (37% vs. 18%, and 5.8 vs. 2.1 months, respectively; P = 0.002).Conclusions: Smoking status, PS, and EGFR mutation/ALK rearrangement were independent predictors of PFS. Our study elucidated nivolumab's efficacy in previously underreported patient populations; i.e., those with poor PS and/or with driver oncogenes. We also found that pneumonitis is not infrequent, and carries key implications for outcomes. These data should be useful for improving the clinical courses of nivolumab-treated patients with NSCLC.