PD-1 阻断联合顺铂为基础的化疗治疗小细胞/神经内分泌膀胱癌和前列腺癌患者。

PD-1 blockade plus cisplatin-based chemotherapy in patients with small cell/neuroendocrine bladder and prostate cancers.

机构信息

Department of Molecular, Cellular and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.

Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.

出版信息

Cell Rep Med. 2024 Nov 19;5(11):101824. doi: 10.1016/j.xcrm.2024.101824. Epub 2024 Nov 12.

Small cell neuroendocrine cancers share biologic similarities across tissue types, including transient response to platinum-based chemotherapy with rapid progression of disease. We report a phase 1b study of pembrolizumab in combination with platinum-based chemotherapy in 15 patients with stage III-IV small cell bladder (cohort 1) or small cell/neuroendocrine prostate cancers (cohort 2). Overall response rate (ORR) is 43% with two-year overall survival (OS) rate of 86% (95% confidence interval [CI]: 0.63, 1.00) for cohort 1 and 57% (95% CI: 0.30, 1.00) for cohort 2. Treatment is tolerated well with grade 3 or higher adverse events occurring in 40% of patients with no deaths or treatment cessation secondary to toxicity. Single-cell and T cell receptor sequencing of serial peripheral blood samples reveals clonal expansion of diverse T cell repertoire correlating with progression-free survival. Our results demonstrate promising efficacy and safety of this treatment combination and support future investigation of this biomarker. This study was registered at ClinicalTrials.gov (NCT03582475).

小细胞神经内分泌癌在组织类型上具有相似的生物学特征，包括对铂类化疗的短暂反应和疾病的快速进展。我们报告了一项 1b 期研究，评估派姆单抗联合铂类化疗在 15 例 III-IV 期小细胞膀胱癌（队列 1）或小细胞/神经内分泌前列腺癌（队列 2）患者中的疗效。队列 1 的总体缓解率（ORR）为 43%，2 年总生存率（OS）为 86%（95%置信区间 [CI]：0.63，1.00），队列 2 的 ORR 为 57%（95% CI：0.30，1.00）。治疗耐受性良好，40%的患者发生 3 级或更高级别的不良事件，但无死亡或因毒性而停止治疗。对连续外周血样本进行单细胞和 T 细胞受体测序显示，多样化的 T 细胞 repertoire 出现克隆扩增，与无进展生存期相关。我们的研究结果表明这种治疗联合具有有前景的疗效和安全性，并支持进一步研究该生物标志物。该研究在 ClinicalTrials.gov 上注册（NCT03582475）。