长期抗 PD-1 治疗（HOT1902）后晚期非小细胞肺癌患者的预后因素。
Prognostic factors in patients with advanced non-small cell lung cancer after long-term Anti-PD-1 therapy (HOT1902).
机构信息
Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
出版信息
Lung Cancer. 2021 Jun;156:12-19. doi: 10.1016/j.lungcan.2021.04.011. Epub 2021 Apr 15.
OBJECTIVES
Limited information is available on the appropriate treatment duration of immune checkpoint inhibitors (ICIs). We aimed to identify candidates who would benefit from ICI discontinuation after one year of treatment for metastatic non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
This retrospective multi-institutional observational study examined medical records of all consecutive patients with advanced or recurrent NSCLC, who started ICI monotherapy at 15 institutions in Japan between December 2015 and December 2017. Patients who received initial ICI therapy for >1 year without progressive disease were defined as the long-term treatment (LT) group; others were defined as the non-long-term treatment (NLT) group. Primary outcomes included the prognostic factors in the LT group, whereas secondary outcomes included efficacy of ICI rechallenge, safety, and survival outcomes in the overall population.
RESULTS
In total, 676 patients were enrolled, and 114 (16.9 %) were assigned to the LT group. The median time interval from the start of initial ICI administration to data cutoff was 34.3 months (range, 24.1-47.8); thus, all surviving patients were followed-up for at least 2 years from the start of initial ICI. Median progression-free survival (PFS) was longer in the LT than in the NLT group (33.6 months vs. 2.7 months; p < 0.001). On multivariate analysis, significantly better PFS was associated with smoking (hazard ratio [HR]=0.36, p = 0.04), and complete response (CR; HR=uncomputable, p < 0.001) in the LT group. Thirty-seven patients (5.5 %) received ICI rechallenge, including 10 in the LT group. Among patients receiving rechallenge treatment, the median PFS was 2.2 months, with no difference between the LT and NLT groups.
CONCLUSIONS
In the LT group, smoking and achieving CR were significantly associated with better PFS. Since rechallenge treatment was not effective, careful consideration is required for discontinuing ICI. However, these prognostic factors are helpful in considering candidates for ICI discontinuation.
TRIAL REGISTRATION
UMIN ID, UMIN000041403.
目的
关于免疫检查点抑制剂（ICI）的适当治疗持续时间，相关信息有限。我们旨在确定在转移性非小细胞肺癌（NSCLC）患者接受一年 ICI 治疗后获益于 ICI 停药的候选者。
材料和方法
本回顾性多机构观察性研究检查了 2015 年 12 月至 2017 年 12 月期间日本 15 个机构接受 ICI 单药治疗的所有连续晚期或复发性 NSCLC 患者的病历。将接受初始 ICI 治疗>1 年且无疾病进展的患者定义为长期治疗（LT）组；其他患者则被定义为非长期治疗（NLT）组。主要结局包括 LT 组的预后因素，次要结局包括总体人群中 ICI 再挑战的疗效、安全性和生存结局。
结果
共有 676 名患者入组，其中 114 名（16.9%）被分配到 LT 组。从初始 ICI 给药开始到数据截止的中位时间间隔为 34.3 个月（范围，24.1-47.8）；因此，所有存活患者均从初始 ICI 开始至少随访 2 年。LT 组的中位无进展生存期（PFS）长于 NLT 组（33.6 个月比 2.7 个月；p<0.001）。多变量分析显示，在 LT 组中，吸烟（风险比[HR]=0.36，p=0.04）和完全缓解（CR；HR=不可计算，p<0.001）与更好的 PFS显著相关。37 名患者（5.5%）接受了 ICI 再挑战，其中 10 名在 LT 组。在接受再挑战治疗的患者中，中位 PFS 为 2.2 个月，LT 组和 NLT 组之间无差异。
结论
在 LT 组中，吸烟和获得 CR 与更好的 PFS 显著相关。由于再挑战治疗无效，因此需要仔细考虑停止 ICI。然而，这些预后因素有助于考虑停止 ICI 的候选者。
试验注册
UMIN ID，UMIN000041403。
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