帕博利珠单抗治疗的早期血清和血液学反应可预测转移性尿路上皮癌的生存情况。

Early Serum and Hematological Responses to Pembrolizumab Therapy as Predictors of Survival in Metastatic Urothelial Cancer.

机构信息

Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan;

Department of Urology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

出版信息

Anticancer Res. 2022 Apr;42(4):2045-2051. doi: 10.21873/anticanres.15685.

DOI:10.21873/anticanres.15685

PMID:35347027

Abstract

BACKGROUND

In order to search for predictive biomarkers of efficacy of pembrolizumab therapy for metastatic urothelial cancer (UC), we investigated the relationship between treatment outcomes and early neutrophil-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and C-reactive protein (CRP) responses.

PATIENTS AND METHODS

Medical records of 101 patients with metastatic UC who started pembrolizumab as a second-line or later treatment were reviewed. NLR, LDH, and CRP were recorded after 3 weeks of therapy. In addition, we investigated whether these factors had an association with prolonged progression-free (PFS) or overall (OS) survival.

RESULTS

The objective response rate, median PFS, and median OS were 25.7%, 6.3 months, and 15.2 months, respectively. PFS and OS were significantly shorter in patients with NLR>3, LDH>upper limit of normal (ULN), and CRP>0.5 mg/dl after 3 weeks of pembrolizumab treatment (p<0.05). A predictive model comprising these factors (favorable risk group: 0 risk factors; intermediate-risk group: 1-2 risk factors; poor-risk group: 3 risk factors) revealed distinct PFS and OS curves (p<0.001). In the favorable risk group, 12-month OS was 79.6%; in the poor-risk group, it was 12.8%. Harrell's C-indices for NLR >3, LDH >ULN, CRP >0.5 mg/dl, and all three combined for predicting OS were 0.656, 0.625, 0.633 and 0.678, respectively. Early responses were also non-significantly associated with ORR (p=0.37).

CONCLUSION

Pembrolizumab treatment outcomes are associated with early NLR, LDH, and CRP responses in metastatic urothelial cancer.

摘要

背景

为了寻找帕博利珠单抗治疗转移性尿路上皮癌（UC）疗效的预测生物标志物，我们研究了治疗结果与早期中性粒细胞-淋巴细胞比值（NLR）、乳酸脱氢酶（LDH）和 C 反应蛋白（CRP）反应之间的关系。

患者和方法

回顾了 101 例转移性 UC 患者的病历，这些患者在二线或二线以上开始接受帕博利珠单抗治疗。在治疗 3 周后记录 NLR、LDH 和 CRP。此外，我们还研究了这些因素是否与延长无进展（PFS）或总（OS）生存时间有关。

结果

客观缓解率、中位 PFS 和中位 OS 分别为 25.7%、6.3 个月和 15.2 个月。在帕博利珠单抗治疗 3 周后，NLR>3、LDH>正常值上限（ULN）和 CRP>0.5mg/dl 的患者的 PFS 和 OS 明显更短（p<0.05）。包含这些因素的预测模型（无风险因素：0 个风险因素；中风险因素：1-2 个风险因素；高风险因素：3 个风险因素）显示出明显的 PFS 和 OS 曲线（p<0.001）。在低风险组中，12 个月的 OS 为 79.6%；在高风险组中，12 个月的 OS 为 12.8%。NLR>3、LDH>ULN、CRP>0.5mg/dl 及三者联合预测 OS 的 Harrell C 指数分别为 0.656、0.625、0.633 和 0.678。早期反应与 ORR 也无显著相关性（p=0.37）。