Association of Tumor Mutational Burden and Microsatellite Instability With Response and Outcomes in Patients With Urothelial Carcinoma Treated With Immune Checkpoint Inhibitor.

Autor: Bakaloudi DR; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA., Talukder R; Department of Medicine, Division of Hematology/Oncology, Baylor College of Medicine, Houston, TX., Makrakis D; Department of Medicine, Jacobi Medical Center-Albert Einstein College of Medicine, Bronx, NY., Diamantopoulos L; Department of Hematology/Oncology, Mayo Clinic, Rochester, MΝ., Enright T; Department of Medicine, University of Washington, Seattle, WA., Leary JB; Department of Medicine, University of Washington, Seattle, WA., Patgunarajah U; Department of Hematology and Oncology, Taussig cancer Institute, Cleveland Clinic Foundation, Cleveland, OH., Thomas VM; Division of Oncology, Department of Medicine, University of Utah, Salt Lake City, UT., Swami U; Division of Oncology, Department of Medicine, University of Utah, Salt Lake City, UT., Agarwal N; Division of Oncology, Department of Medicine, University of Utah, Salt Lake City, UT., Jindal T; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, Helen Diller Family Cancer Center, San Francisco, CA., Koshkin VS; Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, Helen Diller Family Cancer Center, San Francisco, CA., Brown JR; Division of Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH., Barata P; Division of Oncology, University Hospitals Seidman Cancer Center, Cleveland, OH., Murgić J; Department of Oncology and Nuclear Medicine, Sestre milosrdnice University Hospital Center, Zagreb, Croatia; Catholic University of Croatia School of Medicine, Zagreb, Croatia., Miletić M; Department of Oncology and Nuclear Medicine, Sestre milosrdnice University Hospital Center, Zagreb, Croatia., Johnson J; Division of Oncology, Department of Medicine, University of Iowa, Iowa City, IA., Zakharia Y; Division of Oncology, Department of Medicine, University of Iowa, Iowa City, IA., Hui G; Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA., Drakaki A; Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA., Duran I; Department of Oncology, University Hospital Marqués of Valdecilla, Cantabria, Spain., Buznego LA; Department of Oncology, University Hospital Marqués of Valdecilla, Cantabria, Spain., Barrera RM; Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain., Castañeda DM; Department of Medical Oncology, Vall d'Hebron Institute of Oncology, Vall d' Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain., Rey-Cárdenas M; Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain., Castellano D; Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain., Nguyen CB; Division of Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI., Park JJ; Division of Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI., Alva A; Division of Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI., McKay RR; Moores Cancer Center, University of California San Diego, La Jolla, CA., Stewart TF; Moores Cancer Center, University of California San Diego, La Jolla, CA., Epstein IB; Dana-Farber Cancer Institute/Brigham and Women's Hospital Harvard Medical School, Boston, MA., Bellmunt J; Dana-Farber Cancer Institute/Brigham and Women's Hospital Harvard Medical School, Boston, MA., Wright JL; Department of Urology, University of Washington, Seattle, WA., Gupta S; Department of Hematology and Oncology, Taussig cancer Institute, Cleveland Clinic Foundation, Cleveland, OH. Electronic address: Guptas5@ccf.org., Grivas P; Division of Hematology and Oncology, Department of Medicine, University of Washington, Seattle, WA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA. Electronic address: pgrivas@uw.edu., Khaki AR; Division of Oncology, Department of Medicine, Stanford University, Palo Alto, CA. Electronic address: alikhaki@stanford.edu.
Jazyk: angličtina
Zdroj: Clinical genitourinary cancer [Clin Genitourin Cancer] 2024 Aug 12; Vol. 22 (6), pp. 102198. Date of Electronic Publication: 2024 Aug 12.
DOI: 10.1016/j.clgc.2024.102198
Abstrakt: Background: Microsatellite Instability (MSI) and Tumor Mutational Burden (TMB) are associated with immune checkpoint inhibitor (ICI) efficacy. We examined the association between TMB and MSI status with survival in patients with urothelial carcinoma (UC) treated with ICI.
Methods: Patients from 15 institutions were treated with ICI monotherapy. Primary endpoint was overall survival and secondary endpoints included observed response rate (ORR), and progression-free (PFS) calculated from ICI initiation. TMB was analyzed as dichotomous (≥10 vs. <10 mut/Mb) and continuous variable.
Results: We identified 411 patients: 203 were treated with ICI 1L/upfront; 104 with 2 + L. For the 1L/upfront: median [m] OS was numerically longer in patients with TMB ≥10 versus TMB <10: mOS 35 versus 26 months (HR = 0.6) and with MSI-H and MSI-S (mOS NR vs. 22 months), though neither association was statistically significant. A statistically significant association was found between TMB (continuous variable) and OS (HR = 0.96, P = .01). For 2 + L: mOS was numerically longer in patients with TMB ≥10 versus TMB <10: (20 vs. 12 months; HR = 0.9); mOS was 12 and 17 months for patients with MSI-H and MSI-S, respectively. Eighty-nine patients received maintenance avelumab (mAV): mOS was longer in patients with TMB ≥10 versus TMB <10: 61 versus 17 months; (HR = 0.2, P = .02) and with MSI-H and MSI-S (NR vs. 24 months).
Conclusions: Although not reaching statistical significance in several subsets, patients with high TMB and MSI-H had numerically longer OS with ICI, especially with mAV. Further validation is needed.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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