1. Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma
- Author
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Talukder, Rafee, Makrakis, Dimitrios, Lin, Genevieve Ihsiu, Diamantopoulos, Leonidas N, Dawsey, Scott, Gupta, Shilpa, Carril-Ajuria, Lucia, Castellano, Daniel, de Kouchkovsky, Ivan, Jindal, Tanya, Koshkin, Vadim S, Park, Joseph J, Alva, Ajjai, Bilen, Mehmet A, Stewart, Tyler F, McKay, Rana R, Tripathi, Nishita, Agarwal, Neeraj, Vather-Wu, Naomi, Zakharia, Yousef, Morales-Barrera, Rafael, Devitt, Michael E, Cortellini, Alessio, Fulgenzi, Claudia Angela Maria, Pinato, David J, Nelson, Ariel, Hoimes, Christopher J, Gupta, Kavita, Gartrell, Benjamin A, Sankin, Alex, Tripathi, Abhishek, Zakopoulou, Roubini, Bamias, Aristotelis, Murgic, Jure, Fröbe, Ana, Rodriguez-Vida, Alejo, Drakaki, Alexandra, Liu, Sandy, Lu, Eric, Kumar, Vivek, Lorenzo, Giuseppe Di, Joshi, Monika, Isaacsson-Velho, Pedro, Buznego, Lucia Alonso, Duran, Ignacio, Moses, Marcus, Barata, Pedro, Sonpavde, Guru, Wright, Jonathan L, Yu, Evan Y, Montgomery, Robert Bruce, Hsieh, Andrew C, Grivas, Petros, and Khaki, Ali Raza
- Subjects
Cancer ,Clinical Research ,Humans ,Immune Checkpoint Inhibitors ,Carcinoma ,Transitional Cell ,Retrospective Studies ,Cohort Studies ,Treatment Outcome ,Urinary Bladder Neoplasms ,Bladder cancer ,Immunotherapy ,Platinum resistance ,Checkpoint Inhibitor ,Outcomes ,Oncology and Carcinogenesis ,Public Health and Health Services ,Oncology & Carcinogenesis - Abstract
BackgroundEarly 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 methodsWe 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.ResultsWe 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.ConclusionAmong 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.
- Published
- 2022