Objectives

: Understand from a real-world cohort the unique clinical and genomic determinants of a durable response to immune checkpoint inhibitors (ICIs).

Materials and Methods

: This is a retrospective study of patients with NSCLC who received any ICI-based regimen as first or second line therapy. Long-term responders (LTR) achieved an overall survival (OS) ≥ 3 years from time of treatment start, while non-responders (NR) were patients who had an OS of 6-12 months from time of treatment start. Clinical and demographic covariables were collected from electronic medical records. Fisher's exact test and Mann-Whitney test were used to analyze the association of a long-term response to ICI in relation to clinical and genomic variables. All p-values were considered significant at p-value < 0.05.

Results

: A total of 72 patients were included in this study (LTR n=37, NR n=35). There were no significant differences in age, sex, race and BMI between groups. The presence of liver metastases at the time of ICI initiation and PD-L1 status were not associated with LTR to ICIs. Patients in the LTR were more likely to experience irAEs at 3-,6- and 12-months. KRAS mutant tumors were numerically more common in the LTR group (n=13 versus 8).

Conclusion

: We observe no strong clinical and biomarkers of a prolonged response to ICIs. Additional large prospective cohort studies are needed to investigate the genomic footprint of long-term responders.

MicroAbstract

Our retrospective study aims to explore the clinical and genomic underpinnings of a durable response to ICI. We identify lower ECOG performance status at diagnosis, the absence of liver metastases at diagnosis and occurrence of irAEs as predictors of a prolonged response. These findings help inform on therapeutic selection and personalized discussions of benefit to patients with lung cancer.

中文翻译：

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接受免疫检查点阻断治疗转移性非小细胞肺癌长期反应者的临床和基因组特征

目标

：从现实世界的队列中了解免疫检查点抑制剂 (ICIs) 持久反应的独特临床和基因组决定因素。

材料和方法

：这是一项针对接受任何基于 ICI 的方案作为一线或二线治疗的 NSCLC 患者的回顾性研究。长期缓解者 (LTR) 的总生存期 (OS) 自治疗开始起≥ 3 年，而无缓解者 (NR) 是指自治疗开始起 OS 为 6-12 个月的患者。从电子病历中收集临床和人口统计协变量。Fisher 精确检验和 Mann-Whitney 检验用于分析 ICI 长期反应与临床和基因组变量的关联。当 p 值 < 0.05 时，所有 p 值均被视为显着。

结果

：本研究共纳入 72 名患者（LTR n=37，NR n=35）。各组之间的年龄、性别、种族和体重指数没有显着差异。ICI 启动时肝转移的存在和 PD-L1 状态与 ICI 的 LTR 无关。LTR 患者更有可能在 3、6 和 12 个月时出现 irAE。KRAS突变肿瘤在 LTR 组中更为常见（n=13 对 8）。

结论

：我们没有观察到 ICI 长期反应的强临床和生物标志物。需要额外的大型前瞻性队列研究来调查长期反应者的基因组足迹。

微摘要

我们的回顾性研究旨在探索 ICI 持久反应的临床和基因组基础。我们确定诊断时较低的 ECOG 表现状态、诊断时不存在肝转移以及 irAE 的发生作为长期缓解的预测因素。这些发现有助于为肺癌患者的治疗选择和益处的个性化讨论提供信息。