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.
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.
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.
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.
Cancer. 2024 Oct 28 [Epub ahead of print]
Peter H O'Donnell, Yohann Loriot, Tibor Csoszi, Nobuaki Matsubara, Sang Joon Shin, Se Hoon Park, Vagif Atduev, Mahmut Gumus, Saziye Burcak Karaca, Petros Grivas, Ronald de Wit, Daniel E Castellano, Thomas Powles, Jacqueline Vuky, Yujie Zhao, Karen O'Hara, Chinyere E Okpara, Sonia Franco, Blanca Homet Moreno, Jakub Żołnierek, Arlene O Siefker-Radtke
Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA., Early Drug Development Department, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Jász-Nagykun-Szolnok County Hospital, Szolnok, Hungary., Department of Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan., Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea., Division of Hematology/Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Volga District Medical Center, Federal Medical-Biological Agency, Nizhny Novgorod, Russia., Department of Medical Oncology, Istanbul Medeniyet University, Istanbul, Turkey., Ege University Faculty of Medicine, Tülay Aktas Oncology Hospital, Izmir, Turkey., Division of Hematology/Oncology, Department of Medicine, University of Washington, Seattle, Washington, USA., Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands., Department of Medical Oncology, Hospital Universitario 12 de Octubre, GUARD Consortium, Madrid, Spain., Department of Genitourinary Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK., Department of Medicine/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA., Merck & Co, Inc, Rahway, New Jersey, USA., Eisai, Ltd, Hatfield, UK., LUXMED Oncology, Warsaw, Poland., Division of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.