A real-world experience of pembrolizumab monotherapy in microsatellite instability-high and/or tumor mutation burden-high metastatic castration-resistant prostate cancer: outcome analysis.

IF 5.1 2区医学 Q1 ONCOLOGY

Prostate Cancer and Prostatic Diseases Pub Date : 2024-02-10 DOI:10.1038/s41391-024-00799-y

Osama Mosalem, Winston Tan, Alan H Bryce, Roxana S Dronca, Daniel S Childs, Lance C Pagliaro, Jacob J Orme, Adam M Kase

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引用次数: 0

Abstract

Background: The efficacy of pembrolizumab monotherapy in metastatic castration-resistant prostate cancer patients (mCRPC) when stratified by MSI-H and/or TMB-H is poorly defined. Additionally, outcomes based on sequencing source (i.e., tissue or liquid biopsy) have not been well described. We sought to assess outcomes of pembrolizumab monotherapy in patients with mCRPC and compare efficacy based on MSI-H and/or TMB-H when identified by tissue or liquid biopsy.

Methods: A retrospective analysis was performed of mCRPC patients treated at Mayo Clinic with pembrolizumab monotherapy between 2018 and 2023. Objective response rates (ORR), median progression-free survival (mPFS), and overall survival (mOS), were determined by RECIST v1.1 criteria.

Results: Twenty-two patients with mCRPC received pembrolizumab monotherapy for at least 3 cycles for a MSI-H or TMB-H indication. All patients had next generation sequencing (NGS) performed via tissue (n = 11) or liquid (n = 10) biopsy source. The ORR was 50% (27.3% complete response and 22.7% had partial response). The mPFS for TMB 10-14.9 mut/Mb (n = 4), TMB 15-24.9 mut/Mb (n = 6), and TMB ≥ 25 mut/Mb (n = 10) was 2.1, not reached (NR), and NR, respectively (p = 0.0003). The mOS for these same groups was 5.1 months, 20.5 months, and not reached, respectively. Among patients with TMB-H without co-occurring MSI-H or CDK12 (n = 6), none experienced a response and only one patient had stable disease compared to patients with MSI-H (n = 12) for whom the ORR was 75%. Immunotherapy responsive alterations such as ATRX and PTCH1 mutations were frequently noticed among patients who had complete response (CR).

Conclusions: Our hypothesis-generating study suggests that MSI-H drives the efficacy of pembrolizumab in mCRPC with better survival outcomes as TMB increases. Clinicians should consider alternative treatment strategies for advanced prostate cancer when TMB-H is present without co-occurring MSI-H or CDK12.

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pembrolizumab单药治疗微卫星不稳定性高和/或肿瘤突变负荷高的转移性耐阉割前列腺癌的真实世界经验：结果分析。

背景：按MSI-H和/或TMB-H分层的pembrolizumab单药治疗转移性耐药前列腺癌患者（mCRPC）的疗效尚不明确。此外，基于测序来源（即组织或液体活检）的结果也没有得到很好的描述。我们试图评估pembrolizumab单药治疗mCRPC患者的疗效，并比较基于组织或液体活检确定的MSI-H和/或TMB-H的疗效：对2018年至2023年期间在梅奥诊所接受pembrolizumab单药治疗的mCRPC患者进行了回顾性分析。根据RECIST v1.1标准确定客观反应率（ORR）、中位无进展生存期（mPFS）和总生存期（mOS）：22例mCRPC患者因MSI-H或TMB-H适应症接受了至少3个周期的pembrolizumab单药治疗。所有患者均通过组织（11 例）或液体（10 例）活检来源进行了新一代测序 (NGS)。ORR为50%（27.3%完全应答，22.7%部分应答）。TMB 10-14.9突变/Mb（n = 4）、TMB 15-24.9突变/Mb（n = 6）和TMB ≥ 25突变/Mb（n = 10）的mPFS分别为2.1、未达到（NR）和NR（p = 0.0003）。这几组患者的 mOS 分别为 5.1 个月、20.5 个月和未达到。在未同时合并 MSI-H 或 CDK12 的 TMB-H 患者（n = 6）中，没有人出现反应，只有一名患者病情稳定，相比之下，MSI-H 患者（n = 12）的 ORR 为 75%。在获得完全应答（CR）的患者中，ATRX和PTCH1突变等免疫治疗反应性改变经常出现：我们的假设性研究表明，MSI-H可促进pembrolizumab在mCRPC中的疗效，随着TMB的增加，患者的生存率也会提高。临床医生在治疗晚期前列腺癌时，如果出现TMB-H而不同时伴有MSI-H或CDK12，则应考虑其他治疗策略。

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来源期刊

Prostate Cancer and Prostatic Diseases 医学-泌尿学与肾脏学

CiteScore

10.00

自引率

6.20%

发文量

142

审稿时长

6-12 weeks

期刊介绍： Prostate Cancer and Prostatic Diseases covers all aspects of prostatic diseases, in particular prostate cancer, the subject of intensive basic and clinical research world-wide. The journal also reports on exciting new developments being made in diagnosis, surgery, radiotherapy, drug discovery and medical management. Prostate Cancer and Prostatic Diseases is of interest to surgeons, oncologists and clinicians treating patients and to those involved in research into diseases of the prostate. The journal covers the three main areas - prostate cancer, male LUTS and prostatitis. Prostate Cancer and Prostatic Diseases publishes original research articles, reviews, topical comment and critical appraisals of scientific meetings and the latest books. The journal also contains a calendar of forthcoming scientific meetings. The Editors and a distinguished Editorial Board ensure that submitted articles receive fast and efficient attention and are refereed to the highest possible scientific standard. A fast track system is available for topical articles of particular significance.