Purpose

Pembrolizumab-based regimens are conditioned by the expression of PD-L1, but durable response rate is limited by innate and acquired resistance mechanisms. Here, we focus on osteopontin (OPN), an upfront biomarker of senescence, which closely associated with natural history of non-small cell lung cancer (NSCLC).

Methods

Seventy-nine patients eligible to pembrolizumab regimens—alone or in combination with chemotherapy—as first-line treatment of advanced NSCLC were enrolled. Predictive value of OPN toward iRECIST progression disease (PD) was set as first outcome. Secondary ones included performance status (ECOG) at baseline, early (first and best) responses, and overall survival (OS).

Results

High Serum OPN characterized patients with worse ECOG-PS (p = 0.015) at baseline and subjects experienced PD/death at first (OR 1.17 [1.02 to 1.35]; p = 0.030) and best responses (0.04 [0.00 to 0.81]; p = 0.035). OPN was associated with time-to-progression (B -2.74 [−4.46 to −1.01]) and time-to death (−0.13 [−0.20 to −0.05]). Cox regression models unveil a predictive value for iRECIST-PD (HR 1.01 [1.00 to 1.02]; p = −0.005), RECIST-PD (HR 1.01 [1.00 to 1.02]; p = 0.017), and OS (HR 1.02 [1.01 to 1.03]; p = 0.001). These models were internally validated through bootstrap resampling and characterized by relevant discrimination ability at ROC curve analyses.

Conclusion

Baseline levels of serum OPN is closely associated with performance status and short/long term outcomes in patients with advanced NSCLC, which are candidate to pembrolizumab-based regimens. As upfront biomarker of senescence, OPN may pave the way for future studies focusing on senescence patterns in NSCLC.

中文翻译：

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循环骨桥蛋白可预测晚期非小细胞肺癌一线治疗的临床和放射学反应

目的

基于 Pembrolizumab 的治疗方案受 PD-L1 表达的调节，但持久缓解率受到先天和获得性耐药机制的限制。在这里，我们重点关注骨桥蛋白（OPN），这是一种衰老的前期生物标志物，与非小细胞肺癌（NSCLC）的自然史密切相关。

方法

纳入了 79 名符合派姆单抗方案（单独或联合化疗）作为晚期 NSCLC 一线治疗的患者。OPN 对 iRECIST 疾病进展 (PD) 的预测价值被设置为第一个结果。次要因素包括基线时的体能状态 (ECOG)、早期（首次和最佳）反应以及总生存期 (OS)。

结果

高血清 OPN 的特征是基线时 ECOG-PS 较差 ( p  = 0.015) 的患者，受试者首先经历 PD/死亡 (OR 1.17 [1.02 至 1.35]；p  = 0.030) 和最佳缓解 (0.04 [0.00 至 0.81]；p  = 0.035）。OPN 与进展时间 (B -2.74 [−4.46 至 -1.01]) 和死亡时间 (−0.13 [−0.20 至 -0.05]) 相关。Cox 回归模型揭示了 iRECIST-PD（HR 1.01 [1.00 至 1.02]； p  = -0.005）、RECIST-PD（HR 1.01 [1.00 至 1.02]；p  = 0.017）和 OS（HR 1.02 [1.01]）的预测值至 1.03]；p  = 0.001）。这些模型通过自举重采样进行了内部验证，并通过 ROC 曲线分析的相关辨别能力进行了表征。

结论

血清 OPN 的基线水平与晚期 NSCLC 患者的体能状态和短期/长期结果密切相关，这些患者是基于派姆单抗的治疗方案的候选者。作为衰老的前期生物标志物，OPN 可能为未来关注 NSCLC 衰老模式的研究铺平道路。