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

• Type of Material: Article
• Authors: Rafee Talukder, University of Washington; Dimitrios Makrakis, University of Washington; Genevieve I Lin, University of Washington; Leonidas N Diamantopoulos, University of Pittsburgh; Scott Dawsey, CleHospital Universitario, Madrid, Spain; Shilpa Gupta, Cleveland Clinic Foundation; Lucia Carril-Ajuria, Hospital Universitario, Madrid, Spain; Daniel Castellano, Hospital Universitario, Madrid, Spain; Ivan de Kouchkovsky, University of California San Francisco; Tanya Jindal, 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; Nishita Tripathi, University of Utah; Neeraj Agarwal, University of Utah; Naomi Vather-Wu, University of Iowa; Yousef Zakharia, University of Iowa; Rafael Morales-Barrera, Univ Autonoma Barcelona; Michael E Devitt, University of Virginia; Alessio Cortellini, Imperial College London; Claudia AM Fulgenzi, Imperial College London; David J Pinato, Imperial College London; Ariel Nelson, Medical College of Wisconsin; Christopher J Hoimes, Seidman Cancer Center at Case Comprehensive Cancer Center; Kavita Gupta, Montefiore Medical Center; Benjamin A Gartrell, Montefiore Medical Center; Alex Sankin, Montefiore Medical Center; Abhishek Tripathi, University of Oklahoma Health Sciences Center; 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; Eric Lu, University of California Los Angeles; Vivek Kumar, Harvard Medical School; Giuseppe Di Lorenzo, Oncology University of Molise and ASL, Salerno, Italy; Monika Joshi, Penn State Canc Inst; Pedro Isaacsson-Velho, Sidney Kimmel Comprehensive Cancer Center, Baltimore; Lucia Alonso Buznego, Hospital Universitario Marques de Valdecilla. IDIVAL. Santander, Spain; Ignacio Duran, Hospital Universitario Marques de Valdecilla. IDIVAL. Santander, Spain; Marcus Moses, Tulane University; Pedro Barata, Tulane University; Guru Sonpavde, Harvard Medical School; Jonathan L Wright, Fred Hutchinson Cancer Center; Evan Y Yu, University of Washington; Robert Bruce Montgomery, University of Washington; Andrew C Hsieh, University of Washington; Petros Grivas, University of Washington; Ali Raza Khaki, Stanford University
• Language: English
• Date: 2022-12-01
• Publisher: CIG MEDIA GROUP, LP
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Elsevier Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.clgc.2022.08.006
• Title of Journal or Parent Work: CLINICAL GENITOURINARY CANCER
• Volume: 20
• Issue: 6
• Start Page: 558
• End Page: 567
• Keywords: DNA-DAMAGE RESPONSE; Checkpoint Inhibitor; MULTICENTER; Life Sciences & Biomedicine; Science & Technology; Platinum resistance; CISPLATIN; Outcomes; Urology & Nephrology; Oncology; PLATINUM RESISTANCE; COMBINATION; Bladder cancer; PEMBROLIZUMAB; Immunotherapy

Abstract

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.