免疫相关不良反应与纳武利尤单抗治疗非小细胞肺癌疗效的相关性。
Association of Immune-Related Adverse Events With Nivolumab Efficacy in Non-Small-Cell Lung Cancer.
机构信息
Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
Clinical Research Center, Kindai University Hospital, Osaka-Sayama, Japan.
出版信息
JAMA Oncol. 2018 Mar 1;4(3):374-378. doi: 10.1001/jamaoncol.2017.2925.
IMPORTANCE
Immune-related adverse events (irAEs) have been associated with the efficacy of PD-1 (programmed cell death protein 1) inhibitors in patients with melanoma, but whether such an association exists for non-small-cell lung cancer (NSCLC) has remained unknown.
OBJECTIVE
To evaluate the relation of irAEs to nivolumab efficacy in NSCLC.
DESIGN, SETTING, AND PARTICIPANTS: In this study based on landmark and multivariable analyses, a total of 134 patients with advanced or recurrent NSCLC who were treated with nivolumab in the second-line setting or later between December 2015 and August 2016 were identified from a review of medical records from multiple institutions, including a university hospital and community hospitals. Data were updated as of December 31, 2016.
EXPOSURES
The absence or presence of any irAE before the landmark date.
MAIN OUTCOMES AND MEASURES
Kaplan-Meier curves of progression-free survival (PFS) according to the development of irAEs in 6-week landmark analysis were evaluated with the log-rank test as a preplanned primary objective. Overall survival (OS) was similarly evaluated. Multivariable analysis of both PFS and OS was performed with Cox proportional hazard regression models.
RESULTS
In a cohort of 134 patients (median [range] age, 68 [33-85] years; 90 men [67%], 44 women [33%]), irAEs were observed in 69 of the 134 study patients (51%), including 12 patients (9%) with such events of grade 3 or 4, and 24 patients (18%) requiring systemic corticosteroid therapy. In 6-week landmark analysis, median PFS was 9.2 months (95% CI, 4.4 to not reached [NR]) and 4.8 months (95% CI, 3.0 to 7.5) (P = .04) whereas median OS was NR (95% CI, 12.3 to NR) and 11.1 months (95% CI, 9.6 to NR) (P = .01) for patients with or without irAEs, respectively. Multivariable analysis also revealed that irAEs were positively associated with survival outcome, with hazard ratios of 0.525 (95% CI, 0.287 to 0.937; P = .03) for PFS and 0.282 (95% CI, 0.101 to 0.667; P = .003) for OS.
CONCLUSIONS AND RELEVANCE
Development of irAEs was associated with survival outcome of nivolumab treatment in patients with advanced or recurrent NSCLC. Further studies are needed to confirm our findings.
重要性
免疫相关不良反应 (irAEs) 与 PD-1（程序性细胞死亡蛋白 1）抑制剂在黑色素瘤患者中的疗效相关，但这种关联是否存在于非小细胞肺癌 (NSCLC) 中仍不清楚。
目的
评估 irAEs 与 nivolumab 在 NSCLC 中的疗效关系。
设计、地点和参与者：本研究基于里程碑和多变量分析，共纳入 134 名在 2015 年 12 月至 2016 年 8 月期间二线或更后线接受 nivolumab 治疗的晚期或复发性 NSCLC 患者，这些患者来自多个机构的病历回顾，包括一所大学医院和社区医院。数据截至 2016 年 12 月 31 日更新。
暴露
在里程碑日期之前有无任何 irAE。
主要结局和测量
通过对数秩检验评估 6 周里程碑分析中 irAE 发展与无进展生存期 (PFS) 的 Kaplan-Meier 曲线，这是一个预先计划的主要目标。同样评估总生存期 (OS)。通过 Cox 比例风险回归模型对 PFS 和 OS 进行多变量分析。
结果
在 134 名患者的队列中（中位 [范围] 年龄，68 [33-85] 岁；90 名男性 [67%]，44 名女性 [33%]），134 名研究患者中有 69 名（51%）出现 irAEs，包括 12 名（9%）出现 3 级或 4 级事件，24 名（18%）需要全身皮质类固醇治疗。在 6 周的里程碑分析中，中位 PFS 为 9.2 个月（95%CI，4.4 至未达到 [NR]）和 4.8 个月（95%CI，3.0 至 7.5）（P = .04），而中位 OS 为 NR（95%CI，12.3 至 NR）和 11.1 个月（95%CI，9.6 至 NR）（P = .01），分别为有或无 irAEs 的患者。多变量分析还显示，irAEs 与生存结果呈正相关，PFS 的风险比为 0.525（95%CI，0.287 至 0.937；P = .03），OS 的风险比为 0.282（95%CI，0.101 至 0.667；P = .003）。
结论和相关性
irAEs 的发生与晚期或复发性 NSCLC 患者接受 nivolumab 治疗的生存结果相关。需要进一步的研究来证实我们的发现。
Zotero 插件