Julie N. Graff, Christopher J. Hoimes, Winald R. Gerritsen, Ulka N. Vaishampayan, Tony Elliott, Clara Hwang, Albert J. ten Tije, Aurelius Omlin, Raymond S. McDermott, Yves Fradet, Scott T. Tagawa, Deepak Kilari, Cristiano Ferrario, Hiroji Uemura, Robert J. Jones, Satoshi Fukasawa, Avivit Peer, Cuizhen Niu, Christian H. Poehlein, Ping Qiu, Leah Suttner, Ronald de Wit, Charles Schloss, Johann S. de Bono, Emmanuel S. Antonarakis
{"title":"Pembrolizumab联合恩杂鲁胺治疗恩杂鲁胺治疗进展期转移性去势抵抗性前列腺癌：KEYNOTE-199第二阶段研究的第4组和第5组","authors":"Julie N. Graff, Christopher J. Hoimes, Winald R. Gerritsen, Ulka N. Vaishampayan, Tony Elliott, Clara Hwang, Albert J. ten Tije, Aurelius Omlin, Raymond S. McDermott, Yves Fradet, Scott T. Tagawa, Deepak Kilari, Cristiano Ferrario, Hiroji Uemura, Robert J. Jones, Satoshi Fukasawa, Avivit Peer, Cuizhen Niu, Christian H. Poehlein, Ping Qiu, Leah Suttner, Ronald de Wit, Charles Schloss, Johann S. de Bono, Emmanuel S. Antonarakis","doi":"10.1038/s41391-024-00865-5","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study evaluating pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC). Results from cohorts 4 (C4) and 5 (C5) are presented.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Eligible patients had not received chemotherapy for mCRPC and had responded to enzalutamide prior to developing resistance as defined by Prostate Cancer Clinical Trials Working Group 3 guidelines. Patients with RECIST-measurable disease were enrolled in C4, and patients with bone-only or bone-predominant disease were enrolled in C5. All patients received pembrolizumab 200 mg every 3 weeks for ≤35 cycles with ongoing enzalutamide until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate (ORR) per RECIST v1.1 by blinded independent central review in C4. Secondary end points included disease control rate (DCR), overall survival, and safety in each cohort and both cohorts combined.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 126 patients were treated (C4, <i>n</i> = 81; C5, <i>n</i> = 45). Median age was 72 years (range 43–92), and 87.3% had received ≥6 months of enzalutamide prior to study entry. Confirmed ORR was 12.3% (95% CI 6.1–21.5%) for C4. Median duration of response in C4 was 8.1 months (range, 2.5+ to 15.2), and 5 of these patients experienced an objective response lasting ≥6 months. DCR was 53.1% (95% CI 41.7–64.3%) in C4 and 51.1% (95% CI 35.8–66.3%) in C5. Median overall survival was 17.6 months (95% CI 14.0–22.6) in C4 and 20.8 months (95% CI 14.1–28.9) in C5. Grade ≥3 treatment-related adverse events occurred in 35 patients (27.8%); 2 patients in C4 died from immune-related adverse events (myasthenic syndrome and Guillain-Barré syndrome).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The addition of pembrolizumab to ongoing enzalutamide treatment in patients with mCRPC that progressed on enzalutamide after initial response demonstrated modest antitumor activity with a manageable safety profile.</p><h3 data-test=\"abstract-sub-heading\">Clinical trial registry and ID</h3><p>ClinicalTrials.gov, NCT02787005.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":"25 1","pages":""},"PeriodicalIF":5.1000,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer progressing on enzalutamide: cohorts 4 and 5 of the phase 2 KEYNOTE-199 study\",\"authors\":\"Julie N. 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Median age was 72 years (range 43–92), and 87.3% had received ≥6 months of enzalutamide prior to study entry. Confirmed ORR was 12.3% (95% CI 6.1–21.5%) for C4. Median duration of response in C4 was 8.1 months (range, 2.5+ to 15.2), and 5 of these patients experienced an objective response lasting ≥6 months. DCR was 53.1% (95% CI 41.7–64.3%) in C4 and 51.1% (95% CI 35.8–66.3%) in C5. Median overall survival was 17.6 months (95% CI 14.0–22.6) in C4 and 20.8 months (95% CI 14.1–28.9) in C5. 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引用次数: 0
摘要
背景KEYNOTE-199 (NCT02787005)是一项多队列2期研究，评估了pembrolizumab在转移性去势抵抗性前列腺癌（mCRPC）患者中的应用。方法符合条件的患者未接受过mCRPC化疗，并且在出现前列腺癌临床试验工作组3指南定义的耐药性之前对恩杂鲁胺有反应。有RECIST可测量疾病的患者被纳入C4组，有仅骨或骨为主疾病的患者被纳入C5组。所有患者均接受pembrolizumab 200 mg治疗，每3周1次，疗程≤35个周期，并持续服用恩杂鲁胺，直至病情进展、出现不可接受的毒性或停药。主要终点是根据RECIST v1.1标准得出的客观反应率（ORR），由C4盲法独立中央审查。次要终点包括疾病控制率 (DCR)、总生存期以及每个组群和两个组群合并的安全性。结果 共有 126 名患者接受了治疗（C4，n = 81；C5，n = 45）。中位年龄为72岁（43-92岁），87.3%的患者在进入研究前已接受了≥6个月的恩杂鲁胺治疗。C4的确诊ORR为12.3%（95% CI为6.1-21.5%）。C4患者的中位应答持续时间为8.1个月（2.5+至15.2个月），其中5例患者的客观应答持续时间≥6个月。C4和C5患者的DCR分别为53.1%（95% CI 41.7-64.3%）和51.1%（95% CI 35.8-66.3%）。C4患者的中位总生存期为17.6个月（95% CI 14.0-22.6），C5患者为20.8个月（95% CI 14.1-28.9）。35名患者（27.8%）发生了≥3级治疗相关不良事件；2名C4患者死于免疫相关不良事件（肌萎缩综合征和吉兰-巴雷综合征）。结论对于恩杂鲁胺治疗后出现进展的mCRPC患者，在恩杂鲁胺治疗的基础上加用pembrolizumab显示了适度的抗肿瘤活性和可控的安全性。
Pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer progressing on enzalutamide: cohorts 4 and 5 of the phase 2 KEYNOTE-199 study
Background
KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study evaluating pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC). Results from cohorts 4 (C4) and 5 (C5) are presented.
Methods
Eligible patients had not received chemotherapy for mCRPC and had responded to enzalutamide prior to developing resistance as defined by Prostate Cancer Clinical Trials Working Group 3 guidelines. Patients with RECIST-measurable disease were enrolled in C4, and patients with bone-only or bone-predominant disease were enrolled in C5. All patients received pembrolizumab 200 mg every 3 weeks for ≤35 cycles with ongoing enzalutamide until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate (ORR) per RECIST v1.1 by blinded independent central review in C4. Secondary end points included disease control rate (DCR), overall survival, and safety in each cohort and both cohorts combined.
Results
A total of 126 patients were treated (C4, n = 81; C5, n = 45). Median age was 72 years (range 43–92), and 87.3% had received ≥6 months of enzalutamide prior to study entry. Confirmed ORR was 12.3% (95% CI 6.1–21.5%) for C4. Median duration of response in C4 was 8.1 months (range, 2.5+ to 15.2), and 5 of these patients experienced an objective response lasting ≥6 months. DCR was 53.1% (95% CI 41.7–64.3%) in C4 and 51.1% (95% CI 35.8–66.3%) in C5. Median overall survival was 17.6 months (95% CI 14.0–22.6) in C4 and 20.8 months (95% CI 14.1–28.9) in C5. Grade ≥3 treatment-related adverse events occurred in 35 patients (27.8%); 2 patients in C4 died from immune-related adverse events (myasthenic syndrome and Guillain-Barré syndrome).
Conclusions
The addition of pembrolizumab to ongoing enzalutamide treatment in patients with mCRPC that progressed on enzalutamide after initial response demonstrated modest antitumor activity with a manageable safety profile.
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.
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