纳武利尤单抗治疗非小细胞肺癌的免疫相关不良事件与疗效的相关性。
Correlation between immune-related adverse events and efficacy in non-small cell lung cancer treated with nivolumab.
机构信息
Third Department of Internal Medicine, Wakayama Medical University, Japan.
Third Department of Internal Medicine, Wakayama Medical University, Japan.
出版信息
Lung Cancer. 2018 Jan;115:71-74. doi: 10.1016/j.lungcan.2017.11.019. Epub 2017 Nov 21.
OBJECTIVES
Patients treated with nivolumab often experience its unique adverse events, called immune-related adverse events (irAEs). Regarding the mechanisms of immune-checkpoint inhibitors (ICIs), the occurrence of irAEs may also reflect antitumor responses. Here, we report the clinical correlation between irAEs and efficacy in NSCLC patients treated with nivolumab.
MATERIALS AND METHODS
Between December 2015 and February 2017, 38 advanced NSCLC patients were treated in our institution. All the patients were enrolled in our single-institutional, prospective, observational cohort study (UMIN000024414). IrAEs were defined as having a potential immunological basis that required more frequent monitoring and potential intervention. We divided the patients into two groups (irAEs group or no-irAEs group) and evaluated the objective response rate (ORR) and progression-free survival (PFS).
RESULTS
The median age of the patients was 68.5 years (range 49-86 years); male/female ratio was 28/10; squamous/non-squamous cell carcinoma cases were 10/28; performance status was 0-1/2/3, 7/26/5. Among the overall population, ORR was 23.7% and median PFS was 91days. At the data cutoff, 14 irAEs were observed. The most common irAE was interstitial pneumonia (n=5). Other irAEs were hypothyroidism (n=4), hyperthyroidism, hypopituitarism, liver dysfunction, rash, and elevated thyroid stimulating hormone levels (n=1, each). Patients with irAEs had significantly higher ORRs compared with no-irAE patients (63.6% versus 7.4%, p <0.01). Similarly, the PFS among irAE patients was longer (median: not reached [95% confidence interval {CI}: 91days to not applicable]) than no-irAE patients (median 49days [95% CI: 36-127days], hazard ratio [HR] 0.10 [95% CI: 0.02-0.37, p<0.001]). Landmark analysis of patients who achieved PFS ≥60days demonstrated similar tendencies, but this was not significant (HR 0.28 [95% CI: 0.04-1.46], p=0.13).
CONCLUSION
There was a correlation between irAE and efficacy in NSCLC patients treated with nivolumab.
目的
接受纳武利尤单抗治疗的患者常出现其独特的不良反应，称为免疫相关不良反应（irAEs）。关于免疫检查点抑制剂（ICI）的作用机制，irAEs 的发生也可能反映出抗肿瘤反应。在此，我们报告了纳武利尤单抗治疗的非小细胞肺癌（NSCLC）患者的 irAEs 与疗效之间的临床相关性。
材料与方法
2015 年 12 月至 2017 年 2 月，38 例晚期 NSCLC 患者在我院接受治疗。所有患者均被纳入我们的单中心、前瞻性、观察性队列研究（UMIN000024414）。irAEs 的定义为具有潜在免疫基础，需要更频繁的监测和潜在干预的不良反应。我们将患者分为两组（irAEs 组或无 irAEs 组），并评估客观缓解率（ORR）和无进展生存期（PFS）。
结果
患者的中位年龄为 68.5 岁（范围 49-86 岁）；男女比例为 28/10；鳞癌/非鳞癌病例分别为 10/28；体能状态为 0-1/2/3 的分别为 7/26/5。在总体人群中，ORR 为 23.7%，中位 PFS 为 91 天。在数据截止时，观察到 14 例 irAEs。最常见的 irAE 是间质性肺炎（n=5）。其他 irAEs 包括甲状腺功能减退症（n=4）、甲状腺功能亢进症、垂体功能减退症、肝功能障碍、皮疹和促甲状腺激素水平升高（n=1，各 1 例）。有 irAEs 的患者的 ORR 明显高于无 irAE 患者（63.6%对 7.4%，p<0.01）。同样，irAE 患者的 PFS 更长（中位：未达到[95%置信区间（CI）：91 天至不可用]）比无 irAE 患者（中位 49 天[95%CI：36-127 天]），风险比（HR）为 0.10[95%CI：0.02-0.37，p<0.001]）。对达到 PFS≥60 天的患者进行的里程碑分析显示出类似的趋势，但无统计学意义（HR 0.28[95%CI：0.04-1.46]，p=0.13）。
结论
纳武利尤单抗治疗的 NSCLC 患者的 irAE 与疗效之间存在相关性。
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