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

IF 11.7 1区医学 Q1 CELL BIOLOGY Cell Reports Medicine Pub Date : 2024-11-19 Epub Date: 2024-11-12 DOI:10.1016/j.xcrm.2024.101824

Yiqian Gu, Ann Ly, Sara Rodriguez, Hanwei Zhang, Jiyoon Kim, Zhiyuan Mao, Ankush Sachdeva, Nazy Zomorodian, Matteo Pellegrini, Gang Li, Sandy Liu, Alexandra Drakaki, Matthew B Rettig, Arnold I Chin

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Abstract

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).

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小细胞/神经内分泌膀胱癌和前列腺癌患者的 PD-1 阻断剂加顺铂化疗。

小细胞神经内分泌癌在不同组织类型中具有生物学相似性，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pembrolizumab联合铂类化疗的1b期研究，研究对象为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。总体反应率（ORR）为43%，组群1的两年总生存率（OS）为86%（95%置信区间[CI]：0.63, 1.00），组群2的两年总生存率（OS）为57%（95%置信区间[CI]：0.30, 1.00）。治疗耐受性良好，40%的患者会出现3级或更高的不良反应，没有患者因毒性而死亡或停止治疗。连续外周血样本的单细胞和T细胞受体测序显示，不同T细胞群的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组合具有良好的疗效和安全性，并支持未来对这种生物标记物的研究。本研究已在 ClinicalTrials.gov (NCT03582475) 上注册。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Reports Medicine Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)

CiteScore

15.00

自引率

1.40%

发文量

231

审稿时长

40 days

期刊介绍： Cell Reports Medicine is an esteemed open-access journal by Cell Press that publishes groundbreaking research in translational and clinical biomedical sciences, influencing human health and medicine. Our journal ensures wide visibility and accessibility, reaching scientists and clinicians across various medical disciplines. We publish original research that spans from intriguing human biology concepts to all aspects of clinical work. We encourage submissions that introduce innovative ideas, forging new paths in clinical research and practice. We also welcome studies that provide vital information, enhancing our understanding of current standards of care in diagnosis, treatment, and prognosis. This encompasses translational studies, clinical trials (including long-term follow-ups), genomics, biomarker discovery, and technological advancements that contribute to diagnostics, treatment, and healthcare. Additionally, studies based on vertebrate model organisms are within the scope of the journal, as long as they directly relate to human health and disease.