Introduction: With expanding indications for programmed death 1 (PD‐1) axis inhibitors in non–small cell lung cancer (NSCLC), acquired resistance (AR) to these therapies is increasingly being encountered. We sought to characterize clinical patterns of AR to PD‐1 axis inhibitors in patients with advanced NSCLC, and evaluate subsequent outcome and management strategies for such patients. Methods: Patients with NSCLC who developed AR to PD‐1 axis inhibitor therapy initiated between December 2009 and February 2016 at one institution were identified and examined by clinical and radiographic features. AR was defined as progressive disease after initial response by either Response Evaluation Criteria in Solid Tumors v1.1 or immune‐related response criteria. Results: Twenty‐six patients with AR to PD‐1 axis inhibitor therapy were identified and evaluated. Median time to AR was 313 days; the 2‐year survival rate from AR was 70% (95% confidence interval: 0.53–0.92). Twenty patients (77%) experienced AR in lymph nodes (LNs), including 11 patients with LN‐only progression. Twenty‐three (88%) patients had recurrence limited to one (54%) or two (35%) sites of disease. Fourteen patients (54%) continued PD‐1 axis inhibitor therapy beyond progression. Three patients were re‐challenged with the same PD‐1 axis inhibitor after holiday from and progression off therapy, 2 again responded. Fifteen patients (58%) received local therapy to site(s) of AR, 11 continued respective PD‐1 axis inhibitor after local therapy. The 2‐year survival rate from AR among these 15 patients was 92% (95% confidence interval: 0.77–1). Conclusions: Acquired resistance to PD‐1 axis inhibitors is often limited to one or two sites when local therapy and continuation of PD‐1 axis inhibitor therapy can result in prolonged benefit. LN metastases appear to be particularly susceptible sites to AR. When progression of disease following response occurs after holiday from PD‐1 axis inhibitor, re‐challenge can again lead to tumor regression.

中文翻译：

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26 例晚期非小细胞肺癌患者对 PD-1 轴抑制剂获得性耐药的临床特征和处理

简介：随着程序性死亡 1 (PD-1) 轴抑制剂在非小细胞肺癌 (NSCLC) 中的适应症不断扩大，人们越来越多地遇到对这些疗法的获得性耐药 (AR)。我们试图表征晚期 NSCLC 患者中 AR 对 PD-1 轴抑制剂的临床模式，并评估此类患者的后续结果和管理策略。方法：对 2009 年 12 月至 2016 年 2 月期间在一家机构开始接受 AR 至 PD-1 轴抑制剂治疗的 NSCLC 患者进行临床和影像学特征的鉴定和检查。AR 被定义为根据实体瘤 v1.1 中的反应评估标准或免疫相关反应标准的初始反应后进行性疾病。结果：确定并评估了 26 名接受 AR 至 PD-1 轴抑制剂治疗的患者。达到 AR 的中位时间为 313 天；AR 的 2 年生存率为 70%（95% 置信区间：0.53–0.92）。20 名患者 (77%) 在淋巴结 (LN) 中经历了 AR，包括 11 名仅出现 LN 进展的患者。23 名 (88%) 患者的复发仅限于一个 (54%) 或两个 (35%) 疾病部位。14 名患者 (54%) 在进展后继续 PD-1 轴抑制剂治疗。三名患者在休假和停止治疗后再次使用相同的 PD-1 轴抑制剂，2 名患者再次出现反应。15 名患者 (58%) 接受了 AR 部位的局部治疗，11 名患者在局部治疗后继续使用各自的 PD-1 轴抑制剂。这 15 名患者中 AR 的 2 年生存率为 92%（95% 置信区间：0.77-1）。结论：当局部治疗和继续 PD-1 轴抑制剂治疗可导致长期获益时，PD-1 轴抑制剂的获得性耐药通常仅限于一个或两个部位。LN 转移似乎是对 AR 特别敏感的部位。当在 PD-1 轴抑制剂休假后出现反应后疾病进展时，再次挑战可再次导致肿瘤消退。