title: Outcomes in patients with advanced urothelial carcinoma after discontinuation of programmed death (PD)-1 or PD ligand 1 inhibitor therapy.
abstract: To study the subsequent therapy and disease outcomes of patients with advanced urothelial carcinoma (UC) after discontinuation of programmed death-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors.
  
  
  
  We performed a retrospective analysis to examine outcomes and systemic therapy administration after PD-1/PD-L1 inhibitor therapy in patients with advanced UC. Data on demographics and therapy administered were collected from the institutions involved in the study. Univariable Cox regression analyses were performed to examine the clinical factors potentially associated with overall survival (OS) after PD-1/PD-L1 inhibitor therapy.
  
  
  
  Data from 62 patients were available from four institutions, with capture of subsequent therapy and outcomes after checkpoint inhibitor immunotherapy. The median patient age was 65.5 years and 51 patients (82.3%) were male. The median (range) duration of PD-1/PD-L1 inhibitor therapy in 55 patients for whom these data were available was 64 (7-669) days. Of these, 22 patients (35.5%) received post-PD-1/PD-L1 inhibitor therapy through a variety of different chemotherapy regimens (n = 16), chemobiological combination (n = 1), biological agents (n = 4) and immunotherapy (n = 1). The median (range) time from last PD-1/PD-L1 inhibitor therapy to subsequent therapy was 58 (14-242) days. The median OS of all patients after completion of PD-1/PD-L1 inhibitor therapy was 149 days (95% confidence interval [CI]: 75-359). Among those who received some post-PD-1/PD-L1 inhibitor therapy, the median OS was 182 days (95% CI: 121-372), and the median time to progression was 124 days (95% CI: 61-273) from the start of post-PD-1/PD-L1 therapy. Among these 22 patients, the only significant baseline prognostic factor associated with OS was performance status.
  
  
  
  In this dataset, 35.5% of patients with advanced UC received systemic therapy after salvage therapy with PD-1/PD-L1 inhibitors. Outcomes after subsequent therapy appear similar to those historically observed in patients who had not received prior PD-1/PD-L1 inhibitor therapy. Further study of patients receiving post-PD-1/PD-L1 inhibitor therapy is warranted to identify factors associated with outcomes and potentially synergistic sequences.
authors.affiliation: UAB Comprehensive Cancer Center, Birmingham, AL, USA.
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.affiliation: McMaster University, Hamilton, ON, Canada.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.affiliation: Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Mullane
authors.affiliation: Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA.
authors.forename: Ana A
authors.initials: AA
authors.lastname: Ramirez
authors.affiliation: Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Vogelzang
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Necchi
authors.affiliation: Barts Cancer Institute, London, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Powles
authors.affiliation: Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols; D060890:B7-H1 Antigen / Q000037:antagonists & inhibitors*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: PD-1 inhibitors; PD-L1 inhibitors; outcomes; post-progression therapy; urothelial carcinoma