Journal article
Association between sites of metastasis and outcomes with immune checkpoint inhibitors in advanced urothelial carcinoma
Clinical genitourinary cancer, Vol.20(5), pp.e440-e452
10/01/2022
DOI: 10.1016/j.clgc.2022.06.001
PMCID: PMC10257151
PMID: 35778337
Abstract
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.
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.
We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (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.
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.
Immune checkpoint inhibitors are a well-established treatment option for advanced urothelial carcinoma, and biomarkers of response are needed for better patient selection. We show that metastatic disease confined to lymph nodes is associated with better outcomes, while metastases to liver, bone or both are associated with poor outcomes with immune checkpoint inhibitor therapy. Results are hypothesis-generating but relevant to practice.
Details
- Title: Subtitle
- Association between sites of metastasis and outcomes with immune checkpoint inhibitors in advanced urothelial carcinoma
- Creators
- Dimitrios Makrakis - University of WashingtonRafee Talukder - University of WashingtonGenevieve Ihsiu Lin - University of WashingtonLeonidas N. Diamantopoulos - University of PittsburghScott Dawsey - Cleveland ClinicShilpa Gupta - Cleveland ClinicLucia Carril-Ajuria - Hospital Universitario 12 De OctubreDaniel Castellano - Hospital Universitario 12 De OctubreIvan de Kouchkovsky - University of California, San FranciscoVadim S. Koshkin - University of California, San FranciscoJoseph J. Park - University of MichiganAjjai Alva - University of MichiganMehmet A. Bilen - Emory UniversityTyler F. Stewart - University of California San DiegoRana R. McKay - University of California San DiegoNishita Tripathi - University of UtahNeeraj Agarwal - University of UtahNaomi Vather-Wu - Department of Medicine, University of Iowa, Iowa City, IAYousef Zakharia - University of IowaRafael Morales-Barrera - Hebron UniversityMichael E. Devitt - University of VirginiaAlessio Cortellini - Imperial College LondonFulgenzi Claudia Angela Maria - Imperial College LondonDavid J. Pinato - Imperial College LondonAriel Nelson - Medical College of WisconsinChristopher J. Hoimes - Case Western Reserve UniversityKavita Gupta - Montefiore Medical CenterBenjamin A. Gartrell - Montefiore Medical CenterAlex Sankin - Montefiore Medical CenterAbhishek Tripathi - University of Oklahoma Health Sciences CenterRoubini Zakopoulou - National and Kapodistrian University of AthensAristotelis Bamias - National and Kapodistrian University of AthensJure Murgic - Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, ZagrebAna Fröbe - Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, ZagrebAlejo Rodriguez-Vida - Hospital Del MarAlexandra Drakaki - David Geffen School of Medicine at UCLASandy Liu - David Geffen School of Medicine at UCLAEric Lu - David Geffen School of Medicine at UCLAVivek Kumar - Brigham and Women's HospitalGiuseppe Di Lorenzo - University of MoliseMonika Joshi - Pennsylvania State UniversityPedro Isaacsson-Velho - Sidney Kimmel Comprehensive Cancer CenterLucia Alonso Buznego - Marqués de Valdecilla University HospitalIgnacio Duran - Marqués de Valdecilla University HospitalMarcus Moses - University of New OrleansAlbert Jang - University of New OrleansPedro Barata - University of New OrleansGuru Sonpavde - Dana-Farber Cancer InstituteEvan Y. Yu - University of WashingtonRobert Bruce Montgomery - University of WashingtonPetros Grivas - University of WashingtonAli Raza Khaki - Stanford University
- Resource Type
- Journal article
- Publication Details
- Clinical genitourinary cancer, Vol.20(5), pp.e440-e452
- DOI
- 10.1016/j.clgc.2022.06.001
- PMID
- 35778337
- PMCID
- PMC10257151
- NLM abbreviation
- Clin Genitourin Cancer
- ISSN
- 1558-7673
- eISSN
- 1938-0682
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 10/01/2022
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984544623702771
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