Department of Respiratory Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
Department of Respiratory Medicine, Kurashiki Central Hospital, Kurashiki, Japan.
Lung Cancer. 2018 May;119:14-20. doi: 10.1016/j.lungcan.2018.02.017. Epub 2018 Mar 2.
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.
We conducted a 15-center, observational, retrospective cohort study of patients with advanced NSCLC who received nivolumab monotherapy between January and December 2016.
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).
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.
纳武利尤单抗已被证明在先前接受过治疗的晚期非小细胞肺癌（NSCLC）患者中是有效且安全的。然而，对于其在真实世界（即非临床试验）环境中的表现知之甚少。此外，对于不符合临床试验条件的患者或在临床试验中归入较小亚组的患者，纳武利尤单抗的疗效尚不清楚。
我们进行了一项由 15 个中心参与的、观察性的、回顾性队列研究，纳入了 2016 年 1 月至 12 月期间接受纳武利尤单抗单药治疗的晚期 NSCLC 患者。
在纳入我们研究的 613 例患者中，141 例患者的体能状态（PS）较差，106 例患者的 EGFR 突变或 ALK 重排阳性。缓解率和疾病控制率分别为 20%和 44%；估计的 1 年无进展生存期（PFS）为 18%。多变量分析确定从不吸烟、PS 差和 EGFR 突变/ALK 重排是 PFS 的独立负预测因素。报告最多的≥3 级不良事件是肺炎（5%的患者）。严重肺炎（≥3 级）的发生时间明显早于轻度肺炎（1.6 个月与 2.3 个月，P=0.031）。患有肺炎的患者的缓解率和 PFS 均高于无肺炎的患者（37%比 18%，5.8 个月比 2.1 个月，P=0.002）。
吸烟状态、PS 和 EGFR 突变/ALK 重排是 PFS 的独立预测因素。我们的研究阐明了纳武利尤单抗在先前报道较少的患者群体中的疗效；即 PS 较差和/或存在驱动致癌基因的患者。我们还发现肺炎并不少见，对结局有重要影响。这些数据对于改善接受纳武利尤单抗治疗的 NSCLC 患者的临床转归应有所帮助。
