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

• Published in: Cancer Vol. 131; no. 1; pp. e35601 - n/a
• Main Authors: O’Donnell, Peter H., Loriot, Yohann, Csoszi, Tibor, Matsubara, Nobuaki, Shin, Sang Joon, Park, Se Hoon, Atduev, Vagif, Gumus, Mahmut, Karaca, Saziye Burcak, Grivas, Petros, Wit, Ronald, Castellano, Daniel E., Powles, Thomas, Vuky, Jacqueline, Zhao, Yujie, O’Hara, Karen, Okpara, Chinyere E., Franco, Sonia, Homet Moreno, Blanca, Żołnierek, Jakub, Siefker‐Radtke, Arlene O.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2025; John Wiley and Sons Inc
• Subjects: Adult; advanced urothelial carcinoma; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; Antitumor activity; bladder cancer; Carcinoma, Transitional Cell - drug therapy; Carcinoma, Transitional Cell - pathology; Chemotherapy; Criteria; Effectiveness; Female; Humans; Immunotherapy; Male; Middle Aged; Monoclonal antibodies; Original; ORIGINAL ARTICLE; Pembrolizumab; Platinum; platinum ineligibility; Progression-Free Survival; Renal function; Safety; Solid tumors; Survival; Targeted cancer therapy; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; Urologic Neoplasms - drug therapy; Urologic Neoplasms - pathology; Urological cancer; Urothelial carcinoma; pembrolizumab; advanced urothelial carcinoma; platinum ineligibility; bladder cancer; immunotherapy
• ISSN: 0008-543X; 1097-0142; 1097-0142
• DOI: 10.1002/cncr.35601

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. Frontline pembrolizumab monotherapy exhibited clinically meaningful and generally consistent efficacy and safety in patients with advanced urothelial carcinoma categorized as potentially ineligible for platinum‐based chemotherapy, which suggests that it remains a feasible and effective treatment option for these patients.