Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

Dimitrios Makrakis, Rafee Talukder, Genevieve Ihsiu Lin, Leonidas N. Diamantopoulos, Scott Dawsey, Shilpa Gupta, Lucia Carril-Ajuria, Daniel Castellano, Ivan de Kouchkovsky, Vadim S. Koshkin, Joseph J. Park, Ajjai Alva, Mehmet A. Bilen, Tyler F. Stewart, Rana R. McKay, Nishita Tripathi, Neeraj Agarwal, Naomi Vather-Wu, Yousef Zakharia, Rafael Morales-BarreraMichael E. Devitt, Alessio Cortellini, Claudia Angela Maria Fulgenzi, David J. Pinato, Ariel Nelson, Christopher J. Hoimes, Kavita Gupta, Benjamin A. Gartrell, Alex Sankin, Abhishek Tripathi, Roubini Zakopoulou, Aristotelis Bamias, Jure Murgic, Ana Fröbe, Alejo Rodriguez-Vida, Alexandra Drakaki, Sandy Liu, Eric Lu, Vivek Kumar, Giuseppe Di Lorenzo, Monika Joshi, Pedro Isaacsson-Velho, Lucia Alonso Buznego, Ignacio Duran, Marcus Moses, Albert Jang, Pedro Barata, Guru Sonpavde, Evan Y. Yu, Robert Bruce Montgomery, Petros Grivas, Ali Raza Khaki

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. Methods: 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. Results: We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)e440-e452
JournalClinical Genitourinary Cancer
Volume20
Issue number5
DOIs
StatePublished - Oct 2022
Externally publishedYes

Keywords

  • Advanced urothelial carcinoma
  • Bladder cancer
  • Immune checkpoint inhibitors
  • Metastatic cancer
  • Outcomes

ASJC Scopus subject areas

  • Oncology
  • Urology

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