Association of prior local therapy and outcomes with programmed-death ligand-1 inhibitors in advanced urothelial cancer

• Type of Material: Article
• Authors: Dimitrios Makrakis, University of Washington; Rafee Talukder, University of Washington; Leonidas N Diamantopoulos, University of Pittsburgh; Lucia Carril-Ajuria, Hospital Universitario 12 de Octubre; Daniel Castellano, Hospital Universitario 12 de Octubre; Ivan De Kouchkovsky, University of California San Francisco; Vadim S Koshkin, University of California San Francisco; Joseph J Park, University of Michigan; Ajjai Alva, University of Michigan; Mehmet Bilen, Emory University; Tyler F Stewart, University of California San Diego; Rana R McKay, University of California San Diego; Victor S Santos, University of Utah; Neeraj Agarwal, University of Utah; Jayanshu Jain, University of Iowa; Yousef Zakharia, University of Iowa; Rafael Morales-Barrera, Univ Autonoma Barcelona; Michael E Devitt, University of Virginia; Michael Grant, Imperial College London; Mark P Lythgoe, Imperial College London; David J Pinato, Imperial College London; Ariel Nelson, Case Comprehensive Cancer Center; Christopher J Hoimes, Case Comprehensive Cancer Center; Evan Shreck, Montefiore Medical Center; Benjamin A Gartrell, Montefiore Medical Center; Alex Sankin, Montefiore Medical Center; Abhishek Tripathi, Univ Oklahoma; Roubini Zakopoulou, National and Kapodistrian University of Athens; Aristotelis Bamias, National and Kapodistrian University of Athens; Jure Murgic, University Hospital Center Sestre Milosrdnice; Ana Fröbe, University Hospital Center Sestre Milosrdnice; Alejo Rodriguez-Vida, Hospital del Mar Research Institute; Alexandra Drakaki, University of California Los Angeles; Sandy Liu, University of California Los Angeles; Vivek Kumar, Harvard Medical School; Giuseppe Di Lorenzo, Oncology University of Molise and ASL; Monika Joshi, Penn State Cancer Institute; Pedro Isaacsson-Velho, Sidney Kimmel Comprehensive Cancer Center; Lucia Alonso Buznego, Hospital Universitario Marques de Valdecilla; Ignacio Duran, Hospital Universitario Marques de Valdecilla; Marcus Moses, Tulane University; Pedro Barata, Tulane University; Guru Sonpavde, Harvard Medical School; Evan Y Yu, University of Washington; Jonathan L Wright, University of Washington; Petros Grivas, University of Washington; Ali Raza Khaki, University of Washington
• Language: English
• Date: 2021-10-25
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 BJU International.
• Final Published Version (URL): http://dx.doi.org/10.1111/bju.15603
• Title of Journal or Parent Work: BJU INTERNATIONAL
• Volume: 130
• Issue: 5
• Start Page: 592
• End Page: 603
• Keywords: RECURRENCE; bladder cancer; #utuc; CARCINOMA; Life Sciences & Biomedicine; RADICAL CYSTECTOMY; #blcsm; Urology & Nephrology; urinary tract neoplasms; #uroonc; outcomes; Science & Technology; immune checkpoint inhibitors; immunotherapy; urothelial carcinoma; BLADDER-CANCER; #BladderCancer

Abstract

Objectives: 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. Patients and Methods: 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. Results: 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. Conclusion: 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.