Journal article
Association of prior local therapy and outcomes with programmed-death ligand-1 inhibitors in advanced urothelial cancer
BJU international, Vol.130(5), pp.592-603
11/2022
DOI: 10.1111/bju.15603
PMCID: PMC10257152
PMID: 34597472
Abstract
To compare clinical outcomes with programmed-death ligand-1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation therapy (RT) prior to developing metastatic disease.
We performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression-free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first-line and second-line or greater [second-plus line]). Logistic regression was used to compare ORR, while Kaplan-Meier analysis and Cox regression were used for PFS and OS. Multivariable models were adjusted for known prognostic factors.
We included 562 patients (first-line: 342 and second-plus line: 220). There was no difference in outcomes based on prior locoregional treatment among those treated with first-line ICIs. In the second-plus-line setting, prior RS was associated with higher ORR (adjusted odds ratio 2.61, 95% confidence interval [CI]1.19-5.74]), longer OS (adjusted hazard ratio [aHR] 0.61, 95% CI 0.42-0.88) and PFS (aHR 0.63, 95% CI 0.45-0.89) vs no prior RS. This association remained significant when type of prior locoregional treatment (RS and RT) was modelled separately.
Prior RS before developing advanced disease was associated with better outcomes in patients with aUC treated with ICIs in the second-plus-line but not in the first-line setting. While further validation is needed, our findings could have implications for prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include the study's retrospective nature, lack of randomization, and possible selection and confounding biases.
Details
- Title: Subtitle
- Association of prior local therapy and outcomes with programmed-death ligand-1 inhibitors in advanced urothelial cancer
- Creators
- Dimitrios Makrakis - University of Washington Medical CenterRafee Talukder - University of Washington Medical CenterLeonidas N Diamantopoulos - University of PittsburghLucia 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 DiegoVictor S Santos - University of UtahNeeraj Agarwal - University of UtahJayanshu Jain - University of IowaYousef Zakharia - University of IowaRafael Morales-Barrera - Universitat Autònoma de BarcelonaMichael E Devitt - University of VirginiaMichael Grant - Imperial College LondonMark P Lythgoe - Imperial College LondonDavid J Pinato - Imperial College LondonAriel Nelson - Medical College of WisconsinChristopher J Hoimes - Duke Medical CenterEvan Shreck - 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, Zagreb, CroatiaAna Fröbe - Zagreb School of BusinessAlejo Rodriguez-Vida - Hospital Del MarAlexandra Drakaki - University of California, Los AngelesSandy Liu - University of California, Los AngelesVivek Kumar - Brigham and Women's HospitalGiuseppe Di Lorenzo - University of MoliseMonika Joshi - Penn State Milton S. Hershey Medical CenterPedro Isaacsson-Velho - Sidney Kimmel Comprehensive Cancer CenterLucia Alonso Buznego - Instituto de Investigación Marqués de ValdecillaIgnacio Duran - Instituto de Investigación Marqués de ValdecillaMarcus Moses - Tulane UniversityPedro Barata - Tulane UniversityGuru Sonpavde - Dana-Farber Cancer InstituteEvan Y Yu - University of Washington Medical CenterJonathan L Wright - University of WashingtonPetros Grivas - University of Washington Medical CenterAli Raza Khaki - Stanford University
- Resource Type
- Journal article
- Publication Details
- BJU international, Vol.130(5), pp.592-603
- DOI
- 10.1111/bju.15603
- PMID
- 34597472
- PMCID
- PMC10257152
- NLM abbreviation
- BJU Int
- ISSN
- 1464-4096
- eISSN
- 1464-410X
- Grant note
- P30 CA023100 / NCI NIH HHS Wellcome Trust T32 CA009515 / NCI NIH HHS UL1 TR002319 / NCATS NIH HHS
- Language
- English
- Date published
- 11/2022
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984544623502771
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