FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.
We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI. Outcomes (observed response rate [ORR], progression-free and overall survival [PFS, OS]) with ICI were compared between patients with and without FGFR 2/3, MTAP, ERBB2 alterations. We compared ORR using logistic regression and PFS/OS using Cox proportional hazards.
Out of 1,514 patients, 276 (18%), 174 (11%) and 208 (14%) patients had known FGFR2/3, MTAP and ERBB2 alteration status, respectively. and were treated with ICI in 1L or 2 + L. In patients with (vs. without) FGFR2/3 alteration, ORR with ICI was 21% vs. 32% (OR 0.54; [95%CI 0.32-0.91]), PFS was significantly shorter in patients with FGFR2/3 alterations (HR = 1.36 [95%CI 1.03-1.80]; P=0.03); OS was not significantly different (HR = 1.22 [95%CI 0.86-1.47]). In patients with (vs. without) MTAP alteration, ORR with ICI was 25% versus 40% (OR 0.52 [95%CI 0.20-1.38]); PFS and OS were nonsignificantly different. In patients with (vs. without) ERBB2 alteration, ORR with ICI was similar (37% vs. 35%; OR 1.06; 95%CI 0.57-1.97); PFS and OS were significantly longer in patients with ERBB2 alteration [HR 0.63 (95%CI 0.41-0.95); P=0.03; HR 0.66, [95% CI 0.44-0.97]), respectively.
Our results support further evaluation of FGFR2/3, MTAP and ERBB2 alterations as putative biomarkers in patients with aUC treated with ICI.
Clinical genitourinary cancer. 2024 Dec 02 [Epub ahead of print]
Rafee Talukder, Dimitra Rafailia Bakaloudi, Dimitrios Makrakis, Leonidas N Diamantopoulos, Thomas Enright, Jacob B Leary, Ruben Raychaudhuri, Nishita Tripathi, Neeraj Agarwal, Tanya Jindal, Jason R Brown, Yousef Zakharia, Macarena Rey-Cárdenas, Daniel Castellano, Charles B Nguyen, Ajjai Alva, Roubini Zakopoulou, Aristotelis Bamias, Rafael Morales Barrera, David Marmolejo, Alexandra Drakaki, David J Pinato, James Korolewicz, Lucia Alonso Buznego, Ignacio Duran, Clara Castro Carballeira, Rana R McKay, Tyler F Stewart, Shilpa Gupta, Pedro Barata, Evan Y Yu, Vadim S Koshkin, Ali Raza Khaki, Petros Grivas
Department of Medicine, University of Washington, Seattle, WA; Department of Medicine, Section of Hematology and Oncology, Baylor College of Medicine, Houston, TX., Department of Medicine, University of Washington, Seattle, WA., Department of Medicine, Jacobi Medical Center-Albert Einstein College of Medicine, Bronx, NY., Department of Medicine, Northwell Health/Staten Island University Hospital, New York City, NY., Division of Oncology, Department of Medicine, University of Utah, Salt Lake City, UT., Division of Hematology/Oncology, Department of Medicine, Helen Diller Family Cancer Center, University of California San Francisco, San Francisco, CA., Division of Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH., Division of Oncology, Department of Medicine, University of Iowa, Iowa City, IA., Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain., Division of Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI., 2nd Propaedeutic Dept of Internal Medicine, School of Medicine, ATTIKON University Hospital, National and Kapodistrian University of Athens, Athens, Greece., Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain., Division of Hematology/Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA., Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, London, UK; Division of Oncology, Department of Translational Medicine (DIMET), University of Piemonte Orientale, Novara, Italy., Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, London, UK., Department of Oncology, University Hospital Marqués of Valdecilla, IDIVAL Santander, Cantabria, Spain., Moores Cancer Center, University of California San Diego, La Jolla, CA., Department of Hematology and Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH., Department of Medicine, University of Washington, Seattle, WA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA., Division of Oncology, Department of Medicine, Stanford University, Stanford, CA., Department of Medicine, University of Washington, Seattle, WA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA. Electronic address: .