Efficacy and safety of pembrolizumab in patients with advanced urothelial carcinoma deemed potentially ineligible for platinum-containing chemotherapy: Post hoc analysis of KEYNOTE-052 and LEAP-011

IF 6.1 2区医学 Q1 ONCOLOGY

Cancer Pub Date : 2024-10-28 DOI:10.1002/cncr.35601

Peter H. O’Donnell MD, Yohann Loriot MD, PhD, Tibor Csoszi MD, Nobuaki Matsubara MD, Sang Joon Shin MD, Se Hoon Park MD, Vagif Atduev MD, Mahmut Gumus MD, Saziye Burcak Karaca MD, Petros Grivas MD, Ronald de Wit MD, Daniel E. Castellano MD, Thomas Powles MD, Jacqueline Vuky MD, Yujie Zhao PhD, Karen O’Hara MBChB, Chinyere E. Okpara PhD, Sonia Franco MD, Blanca Homet Moreno MD, Jakub Żołnierek MD, Arlene O. Siefker-Radtke MD

{"title":"Efficacy and safety of pembrolizumab in patients with advanced urothelial carcinoma deemed potentially ineligible for platinum-containing chemotherapy: Post hoc analysis of KEYNOTE-052 and LEAP-011","authors":"Peter H. O’Donnell MD, Yohann Loriot MD, PhD, Tibor Csoszi MD, Nobuaki Matsubara MD, Sang Joon Shin MD, Se Hoon Park MD, Vagif Atduev MD, Mahmut Gumus MD, Saziye Burcak Karaca MD, Petros Grivas MD, Ronald de Wit MD, Daniel E. Castellano MD, Thomas Powles MD, Jacqueline Vuky MD, Yujie Zhao PhD, Karen O’Hara MBChB, Chinyere E. Okpara PhD, Sonia Franco MD, Blanca Homet Moreno MD, Jakub Żołnierek MD, Arlene O. Siefker-Radtke MD","doi":"10.1002/cncr.35601","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>First-line pembrolizumab monotherapy is a standard of care for platinum-ineligible patients with advanced urothelial carcinoma (UC). No global standardized definition of platinum ineligibility exists. This study aimed to evaluate the efficacy and safety of pembrolizumab monotherapy in patients with UC who met various criteria for platinum ineligibility.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Patients from KEYNOTE-052 and LEAP-011 deemed potentially platinum ineligible were pooled for this post hoc exploratory analysis as follows: group 1: Eastern Cooperative Oncology Group performance status (ECOG PS) 2; group 2: ECOG PS 2 and age ≥80 years, renal dysfunction, or visceral disease; and group 3: any two other factors regardless of ECOG PS. Patients received pembrolizumab 200 mg intravenously every 3 weeks. End points included objective response rate (ORR), progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1, by blinded independent central review, overall survival (OS), and safety.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A total of 612 patients treated with pembrolizumab from KEYNOTE-052 (<i>n</i> = 370) and LEAP-011 (<i>n</i> = 242) were included; the median (range) follow-up was 56.3 months (51.2–65.3 months) and 12.8 months (0.2–25.1 months), respectively. For group 1, ORR was 26.2%, median PFS was 2.7 months, and median OS was 10.1 months. For group 2, ORR ranged from 23.5% to 33.3%, median PFS ranged from 2.1 to 4.4 months, and median OS ranged from 9.1 to 10.1 months. For group 3, ORR ranged from 25.7% to 27.9%, median PFS ranged from 2.1 to 2.8 months, and median OS ranged from 9.0 to 10.6 months. Treatment-related adverse event rates were consistent across groups.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Frontline pembrolizumab has consistent antitumor activity and safety in patients with advanced UC categorized as potentially ineligible for platinum-based chemotherapy, regardless of the variable definitions of platinum ineligibility used.</p>\n </section>\n </div>","PeriodicalId":138,"journal":{"name":"Cancer","volume":"131 1","pages":""},"PeriodicalIF":6.1000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694235/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cncr.35601","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

First-line pembrolizumab monotherapy is a standard of care for platinum-ineligible patients with advanced urothelial carcinoma (UC). No global standardized definition of platinum ineligibility exists. This study aimed to evaluate the efficacy and safety of pembrolizumab monotherapy in patients with UC who met various criteria for platinum ineligibility.

Methods

Patients from KEYNOTE-052 and LEAP-011 deemed potentially platinum ineligible were pooled for this post hoc exploratory analysis as follows: group 1: Eastern Cooperative Oncology Group performance status (ECOG PS) 2; group 2: ECOG PS 2 and age ≥80 years, renal dysfunction, or visceral disease; and group 3: any two other factors regardless of ECOG PS. Patients received pembrolizumab 200 mg intravenously every 3 weeks. End points included objective response rate (ORR), progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1, by blinded independent central review, overall survival (OS), and safety.

Results

A total of 612 patients treated with pembrolizumab from KEYNOTE-052 (n = 370) and LEAP-011 (n = 242) were included; the median (range) follow-up was 56.3 months (51.2–65.3 months) and 12.8 months (0.2–25.1 months), respectively. For group 1, ORR was 26.2%, median PFS was 2.7 months, and median OS was 10.1 months. For group 2, ORR ranged from 23.5% to 33.3%, median PFS ranged from 2.1 to 4.4 months, and median OS ranged from 9.1 to 10.1 months. For group 3, ORR ranged from 25.7% to 27.9%, median PFS ranged from 2.1 to 2.8 months, and median OS ranged from 9.0 to 10.6 months. Treatment-related adverse event rates were consistent across groups.

Conclusions

Frontline pembrolizumab has consistent antitumor activity and safety in patients with advanced UC categorized as potentially ineligible for platinum-based chemotherapy, regardless of the variable definitions of platinum ineligibility used.

查看原文本刊更多论文

pembrolizumab对被认为可能不适合接受含铂化疗的晚期尿路癌患者的疗效和安全性：对KEYNOTE-052和LEAP-011的事后分析。

背景：对于不符合铂治疗条件的晚期尿路上皮癌（UC）患者来说，一线pembrolizumab单药治疗是一种标准治疗方法。目前尚无全球统一的铂类不合格定义。本研究旨在评估符合各种铂类不合格标准的UC患者接受pembrolizumab单药治疗的疗效和安全性：将KEYNOTE-052和LEAP-011中被认为可能不符合铂类治疗条件的患者集中起来进行这项事后探索性分析，具体如下：第1组：东部合作肿瘤学组表现状态（ECOG PS）2；第2组：ECOG PS 2和年龄≥80岁、肾功能障碍或内脏疾病；第3组：任何其他两个因素，无论ECOG PS如何。患者每3周静脉注射200毫克pembrolizumab。终点包括客观反应率（ORR）、根据《实体瘤反应评估标准》1.1版通过盲法独立中央审查得出的无进展生存期（PFS）、总生存期（OS）和安全性：KEYNOTE-052（370例）和LEAP-011（242例）共纳入612例接受过pembrolizumab治疗的患者；随访中位数（范围）分别为56.3个月（51.2-65.3个月）和12.8个月（0.2-25.1个月）。第 1 组的 ORR 为 26.2%，中位 PFS 为 2.7 个月，中位 OS 为 10.1 个月。第2组的ORR为23.5%至33.3%，中位PFS为2.1至4.4个月，中位OS为9.1至10.1个月。第3组的ORR为25.7%至27.9%，中位PFS为2.1至2.8个月，中位OS为9.0至10.6个月。各组的治疗相关不良事件发生率一致：无论铂类化疗不合格的定义如何变化，前线pembrolizumab对归类为可能不符合铂类化疗条件的晚期UC患者具有一致的抗肿瘤活性和安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cancer 医学-肿瘤学

CiteScore

13.10

自引率

3.20%

发文量

480

审稿时长

2-3 weeks

期刊介绍： The CANCER site is a full-text, electronic implementation of CANCER, an Interdisciplinary International Journal of the American Cancer Society, and CANCER CYTOPATHOLOGY, a Journal of the American Cancer Society. CANCER publishes interdisciplinary oncologic information according to, but not limited to, the following disease sites and disciplines: blood/bone marrow; breast disease; endocrine disorders; epidemiology; gastrointestinal tract; genitourinary disease; gynecologic oncology; head and neck disease; hepatobiliary tract; integrated medicine; lung disease; medical oncology; neuro-oncology; pathology radiation oncology; translational research