Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

• Type of Material: Article
• Authors: Dimitrios Makrakis, University of Washington School of Medicine; Rafee Talukder, University of Washington School of Medicine; Genevieve I Lin, University of Washington; Leonidas N Diamantopoulos, University of Pittsburgh School of Medicine; Scott Dawsey, Taussig Cancer Center; Shilpa Gupta, Taussig Cancer Center; Lucia Carril-Ajuria, Hospital Universitario 12 de Octubre; Daniel Castellano, Hospital Universitario 12 de Octubre; Ivan de Kouchkovsky, UCSF School of Medicine; Vadim S Koshkin, UCSF School of Medicine; Joseph J Park, University of Michigan Medical School; Ajjai Alva, University of Michigan Medical School; Mehmet Bilen, Emory University; Tyler F Stewart, University of California San Diego; Rana R McKay, University of California San Diego; Nishita Tripathi, University of Utah School of Medicine; Neeraj Agarwal, University of Utah School of Medicine; Naomi Vather-Wu, University of Iowa; Yousef Zakharia, University of Iowa; Rafael Morales-Barrera, Vall d‘Hebron Institut de Oncologia; Michael E Devitt, University of Virginia School of Medicine; Alessio Cortellini, Imperial College London; Claudia Angela Maria Fulgenzi, Imperial College London; David J Pinato, Imperial College London; Ariel Nelson, Medical College of Wisconsin; Christopher J Hoimes, Case Western Reserve University; Kavita Gupta, Montefiore Medical Center; Benjamin A Gartrell, Montefiore Medical Center; Alex Sankin, Montefiore Medical Center; Abhishek Tripathi, University of Oklahoma Health Sciences Center; Roubini Zakopoulou, University of Athens; Aristotelis Bamias, Attikon University Hospital; Jure Murgic, Sestre milosrdnice University Hospital Canter; Ana Fröbe, Sestre milosrdnice University Hospital Canter; Alejo Rodriguez-Vida, Hospital del Mar; Alexandra Drakaki, David Geffen School of Medicine at UCLA; Sandy Liu, David Geffen School of Medicine at UCLA; Eric Lu, David Geffen School of Medicine at UCLA; Vivek Kumar, Harvard Medical School; Guiseppe D Lorenzo, Università degli Studi del Molise; Monika Joshi, Penn State Cancer Institute; Pedro Isaacsson-Velho, The Sidney Kimmel Comprehensive Cancer Center; Lucia A Buznego, Hospital Universitario Marqués de Valdecilla; Ignacio Duran, Hospital Universitario Marqués de Valdecilla; Marcus Moses, Tulane University; Albert Jang, Tulane University; Pedro Barata, Tulane University; Guru Sonpavde, Harvard Medical School; Evan Y Yu, University of Washington School of Medicine; Robert Bruce Montgomery, University of Washington School of Medicine; Petros Grivas, University of Washington School of Medicine; Ali Raza Khaki, Stanford University
• Language: English
• Date: 2022-10-01
• Publisher: Elsevier Inc.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.clgc.2022.06.001
• Title of Journal or Parent Work: Clinical Genitourinary Cancer
• Volume: 20
• Issue: 5
• Start Page: e440
• End Page: e452
• Keywords: Carcinoma, Transitional Cell; Liver Neoplasms; Metastatic cancer; Retrospective Studies; Advanced urothelial carcinoma; Outcomes; Humans; Immune Checkpoint Inhibitors; Immune checkpoint inhibitors; Urinary Bladder Neoplasms; Bladder cancer

Abstract

Background: Sites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI. Methods: We identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd+ line. Results: We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd+ line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd+ line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant. Conclusion: Bone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.