Xu Yanjun, Li Hui, Fan Yun
Department of Medical Thoracic Oncology, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Hangzhou, China.
Front Oncol. 2021 Mar 5;11:642883. doi: 10.3389/fonc.2021.642883. eCollection 2021.
Immune checkpoint inhibitors (ICIs) have changed the management of non-small cell lung cancer (NSCLC). However, resistance is inevitable. The disease progression patterns, sequential treatment, and prognosis beyond ICI resistance are not completely understood.
We retrospectively analyzed stage IV NSCLC patients who underwent ICI treatment at Zhejiang Cancer Hospital between January 2016 and January 2020 and who suffered disease progression after at least stable disease on immunotherapy for more than 3 months (at least two cycles). Oligoprogression and systematic progression were defined as previous reports. The main outcome measures were progression-free survival (PFS), second PFS (PFS2), and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazards model was used for multivariate analysis.
Totally 1,014 NSCLC patients were administered immunotherapy. Of them, 208 NSCLC patients were included in this retrospective study. The estimated PFS, PFS2 and OS were 6.3 months (95% CI 5.6-7.0 months), 10.7 months (95% CI 10.1-12.7 months), and 21.4 months (95% CI 20.6-26.4 months), respectively. After resistance, 55.3% (N = 115) patients developed oligoprogression, and 44.7% (N = 93) systemic progression. For patients with systemic progression, chemotherapy (N = 35, 37.6%), best supportive care (N = 30, 32.3%), and antiangiogenic therapy alone (N = 11, 11.8%) were the major strategies. A combination of local radiotherapy (N = 38, 33.0%) with continued ICIs was the most common treatment used in oligoprogression group, followed by continued immunotherapy with antiangiogenic therapy (N = 19, 16.5%) and local radiotherapy only (N = 17, 14.9%). For patients with oligoprogression, continued immunotherapy plus local radiotherapy can lead to a significantly longer PFS2 (12.9 10.0 months; = 0.006) and OS (26.3 18.5 months, = 0.001). The PFS2 and OS of patients with oligoprogression were superior to those of patients with systemic progression (PFS2: 13.1 10.0 months, = 0.001; OS: 25.8 . 19.1 months, = 0.003).
The major progression pattern after acquired resistance from immunotherapy is oligoprogression. Local radiotherapy with continued immunotherapy beyond oligoprogression in responders was feasible and led to prolonged PFS2 and OS in advanced NSCLC patients.
免疫检查点抑制剂（ICI）改变了非小细胞肺癌（NSCLC）的治疗方式。然而，耐药是不可避免的。ICI耐药后的疾病进展模式、序贯治疗及预后尚未完全明确。
我们回顾性分析了2016年1月至2020年1月在浙江省肿瘤医院接受ICI治疗、且在免疫治疗至少3个月（至少两个周期）病情稳定后出现疾病进展的IV期NSCLC患者。寡进展和系统性进展的定义如既往报道。主要观察指标为无进展生存期（PFS）、第二次无进展生存期（PFS2）和总生存期（OS）。采用Kaplan-Meier法绘制生存曲线。使用Cox比例风险模型进行多因素分析。
共有1014例NSCLC患者接受了免疫治疗。其中，208例NSCLC患者纳入本回顾性研究。估计的PFS、PFS2和OS分别为6.3个月（95%CI 5.6 - 7.0个月）、10.7个月（95%CI 10.1 - 12.7个月）和21.4个月（95%CI 20.6 - 26.4个月）。耐药后，55.3%（N = 115）的患者出现寡进展，44.7%（N = 93）出现系统性进展。对于系统性进展的患者，化疗（N = 35，37.6%）、最佳支持治疗（N = 30，32.3%）和单纯抗血管生成治疗（N = 11，11.8%）是主要治疗策略。局部放疗联合继续使用ICI（N = 38，33.0%）是寡进展组最常用的治疗方法，其次是继续免疫治疗联合抗血管生成治疗（N = 19，16.5%）和单纯局部放疗（N = 17，14.9%）。对于寡进展患者，继续免疫治疗加局部放疗可使PFS2显著延长（12.9对10.0个月；P = 0.006）和OS显著延长（26.3对18.5个月，P = 0.001）。寡进展患者的PFS2和OS优于系统性进展患者（PFS2：13.1对10.0个月，P = 0.001；OS：25.8对19.1个月，P = 0.003）。
免疫治疗获得性耐药后的主要进展模式是寡进展。对有反应的患者在寡进展后继续免疫治疗联合局部放疗是可行的，并可延长晚期NSCLC患者的PFS2和OS。
