University of Miami, Miller School of Medicine, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Br J Cancer. 2020 Feb;122(3):340-347. doi: 10.1038/s41416-019-0643-y. Epub 2019 Nov 25.
Accessible biomarkers are needed for immunotherapy in advanced non-small-cell lung cancer (NSCLC). We previously described a multivariate risk prediction model, the iSEND, which categorises advanced NSCLC patients treated with nivolumab into Good, Intermediate or Poor groups. This model was developed by using only clinical and analytical variables (sex, ECOG-performance status, neutrophil-to-lymphocyte ratio [NLR] and post-treatment delta NLR).
An international database of 439 patients who received post-platinum PD-1/L1 monotherapies was collected for validation. Performance of the iSEND to different PD-L1 groups was compared by using time-dependent positive predictive value (PPV) for their mortality events.
Median follow-up was 18.2 months (95% CI: 15.9-19.6). The overall survival of the iSEND Good (HR = 0.31, 95% CI: 0.22-0.43, p < 0.0001) was superior to the iSEND Poor. Time-dependent PPV for mortality of iSEND Poor was superior to PD-L1 = 0% group at 12 (75 vs. 53%, p = 0.01) and 18 months (85 vs. 46%, p = 0.03). However, female gender did not independently associate with better outcome in the validation cohort.
The iSEND model is associated with the outcome of post-platinum PD-1/L1 monotherapy in advanced NSCLC patients. The iSEND Poor demonstrated a superior performance to PD-L1 = 0% in negative prognostication. Prospective investigation and modelling with other significant parameters in a larger cohort are warranted.
晚期非小细胞肺癌（NSCLC）的免疫治疗需要可及的生物标志物。我们之前描述了一个多变量风险预测模型 iSEND，该模型将接受纳武利尤单抗治疗的晚期 NSCLC 患者分为良好、中等或不良组。该模型是通过仅使用临床和分析变量（性别、ECOG 表现状态、中性粒细胞与淋巴细胞比值[NLR]和治疗后 delta NLR）开发的。
收集了一个接受铂类后 PD-1/L1 单药治疗的 439 例患者的国际数据库进行验证。通过时间依赖性阳性预测值（PPV）比较 iSEND 在不同 PD-L1 组中的性能，以预测其死亡事件。
中位随访时间为 18.2 个月（95%CI：15.9-19.6）。iSEND 良好组（HR=0.31，95%CI：0.22-0.43，p<0.0001）的总生存期优于 iSEND 不良组。iSEND 不良组的死亡率时间依赖性 PPV 在 12 个月（75%比 53%，p=0.01）和 18 个月（85%比 46%，p=0.03）时优于 PD-L1=0%组。然而，在验证队列中，女性性别与更好的结局并不独立相关。
iSEND 模型与晚期 NSCLC 患者铂类后 PD-1/L1 单药治疗的结局相关。在预后不良方面，iSEND 不良组比 PD-L1=0%组表现更好。需要在更大的队列中进行前瞻性研究和建模，并纳入其他重要参数。
