Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma

Rafee Talukder, Dimitrios Makrakis, Genevieve Ihsiu Lin, Leonidas N. Diamantopoulos, Scott Dawsey, Shilpa Gupta, Lucia Carril-Ajuria, Daniel Castellano, Ivan de Kouchkovsky, Tanya Jindal, 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 ZakhariaRafael Morales-Barrera, Michael 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, Pedro Barata, Guru Sonpavde, Jonathan L. Wright, Evan Y. Yu, Robert Bruce Montgomery, Andrew C. Hsieh, Petros Grivas, Ali Raza Khaki

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background: Early progression on first-line (1L) platinum-based therapy or between therapy lines may be a surrogate of more aggressive disease and poor outcomes in advanced urothelial carcinoma (aUC), but its prognostic role regarding immune checkpoint inhibitor (ICI) response and survival is unclear. We hypothesized that shorter time until start of second-line (2L) ICI would be associated with worse outcomes in aUC. Patients and Methods: We performed a retrospective multi-institution cohort study in patients with aUC treated with 1L platinum-based chemotherapy, who received 2L ICI. Patients receiving switch maintenance ICI were excluded. We defined time to 2L ICI therapy as the time between the start of 1L platinum-based chemotherapy to the start of 2L ICI and categorized patients a priori into 1 of 3 groups: less than 3 months versus 3-6 months versus more than 6 months. We calculated overall response rate (ORR) with 2L ICI, progression-free survival (PFS) and overall survival (OS) from the start of 2L ICI. ORR was compared among the 3 groups using multivariable logistic regression, and PFS, OS using cox regression. Multivariable models were adjusted for known prognostic factors. Results: We included 215, 215, and 219 patients in the ORR, PFS, and OS analyses, respectively, after exclusions. ORR difference did not reach statistical significance between patients with less than 3 months versus 3-6 months versus more than 6 months to 2L ICI. However, PFS (HR 1.64; 95% CI 1.02-2.63) and OS (HR 1.77; 95% CI 1.10-2.84) was shorter among those with time to 2L ICI less than 3 months compared to those who initiated 2L ICI more than 6 months. Conclusion: Among patients with aUC treated with 2L ICI, time to 2L ICI less than 3 months was associated with lower, but not significantly different ORR, but shorter PFS and OS compared to 2L ICI more than 6 months. This highlights potential cross resistance mechanisms between ICI and platinum-based chemotherapy.

Original languageEnglish (US)
Pages (from-to)558-567
Number of pages10
JournalClinical Genitourinary Cancer
Issue number6
StatePublished - Dec 2022


  • Bladder cancer
  • Checkpoint Inhibitor
  • Immunotherapy
  • Outcomes
  • Platinum resistance

ASJC Scopus subject areas

  • Oncology
  • Urology


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