Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy; Tianjin's Clinical Research Center for Cancer; Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.
Division of Thoracic Oncology, Jilin Cancer Hospital, Changchun, China.
Thorac Cancer. 2020 May;11(5):1170-1179. doi: 10.1111/1759-7714.13370. Epub 2020 Mar 5.
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). While rapid progression (RP) has been proposed as a non-negligible pattern of response to ICIs, its definition and related factors remain unclear. This study aimed to develop a clinical definition of RP and to identify related factors.
We retrospectively evaluated Chinese patients who had received an ICI as second-line or later treatment for locally advanced or metastatic NSCLC at a single center. We defined RP as radiological progression at the first response assessment (<2 months after starting the ICI), as well as confirmation of progressive disease or cancer-related death occurring at <3 months. The clinical outcomes were compared for patients with RP or non-RP to identify prognostic factors.
The study evaluated 74 eligible patients with detailed records regarding their ICI therapy, including 25 patients (33.8%) who had experienced RP. Relative to patients with non-RP, patients with RP had significantly shorter median progression-free survival (1.7 months [95% CI: 1.4-2.0 months] vs. 6.3 months [95% CI 5.2-7.3 months], P < 0.001; hazard ratio: 0.14, 95% CI: 0.08-0.25) and significantly shorter median overall survival (8.2 months [95% CI 3.0-13.4 months] vs. 22.6 months [95% CI 17.0-28.1 months], P < 0.001; hazard ratio: 0.27, 95% CI: 0.15-0.49). Multivariate analysis revealed that RP was independently predicted by the presence of ≥3 metastatic sites (P = 0.039) and a neutrophil-to-lymphocyte ratio of ≥3 (P = 0.044).
Among NSCLC patients, RP was a common response to ICI monotherapy and was associated with dramatically reduced progression-free and overall survival. Care is needed when selecting ICI monotherapy for these patients, especially if they have ≥3 metastatic sites or a neutrophil-to-lymphocyte ratio of ≥3.
Significant findings of the study: Patients with rapid progression after immune checkpoint inhibitor monotherapy had poor survival outcomes. The number of metastatic sites and the neutrophil-to-lymphocyte ratio may independently predict treatment response in this setting.
This is the first study to evaluate rapid progression after second-line or later single-agent immunotherapy in a Chinese population. Our findings may help establish effective immunotherapy strategies for NSCLC.
免疫检查点抑制剂（ICIs）已经彻底改变了非小细胞肺癌（NSCLC）的治疗方式。虽然快速进展（RP）已被提出为对 ICI 反应的一种不可忽视的模式，但它的定义和相关因素仍不清楚。本研究旨在制定 RP 的临床定义，并确定相关因素。
我们回顾性评估了在一家单中心接受 ICI 二线或以上治疗的局部晚期或转移性 NSCLC 中国患者。我们将 RP 定义为首次影像学评估时（ICI 开始后<2 个月）发生的放射学进展，以及<3 个月时发生的疾病进展或癌症相关死亡的确认。比较 RP 患者与非 RP 患者的临床结局，以确定预后因素。
本研究共评估了 74 例符合条件的患者，详细记录了他们的 ICI 治疗情况，包括 25 例（33.8%）RP 患者。与非 RP 患者相比，RP 患者的中位无进展生存期明显更短（1.7 个月[95%CI：1.4-2.0 个月] vs. 6.3 个月[95%CI：5.2-7.3 个月]，P<0.001；风险比：0.14，95%CI：0.08-0.25），中位总生存期也明显更短（8.2 个月[95%CI：3.0-13.4 个月] vs. 22.6 个月[95%CI：17.0-28.1 个月]，P<0.001；风险比：0.27，95%CI：0.15-0.49）。多变量分析显示，RP 与存在≥3 个转移部位（P=0.039）和中性粒细胞与淋巴细胞比值≥3（P=0.044）独立相关。
在 NSCLC 患者中，RP 是 ICI 单药治疗的常见反应，与无进展生存期和总生存期明显缩短相关。在为这些患者选择 ICI 单药治疗时需要谨慎，特别是当患者存在≥3 个转移部位或中性粒细胞与淋巴细胞比值≥3 时。
本研究的重要发现：接受免疫检查点抑制剂单药治疗后快速进展的患者生存结局较差。转移部位数量和中性粒细胞与淋巴细胞比值可能独立预测该治疗环境下的治疗反应。
这是第一项评估二线或以上单药免疫治疗后中国人群中快速进展的研究。我们的研究结果可能有助于为 NSCLC 制定有效的免疫治疗策略。
