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

Publication ,  Journal Article
Talukder, R; Makrakis, D; Lin, GI; Diamantopoulos, LN; Dawsey, S; Gupta, S; Carril-Ajuria, L; Castellano, D; de Kouchkovsky, I; Jindal, T ...
Published in: Clin Genitourin Cancer
December 2022

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.

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Published In

Clin Genitourin Cancer

DOI

EISSN

1938-0682

Publication Date

December 2022

Volume

20

Issue

6

Start / End Page

558 / 567

Location

United States

Related Subject Headings

  • Urinary Bladder Neoplasms
  • Treatment Outcome
  • Retrospective Studies
  • Oncology & Carcinogenesis
  • Immune Checkpoint Inhibitors
  • Humans
  • Cohort Studies
  • Carcinoma, Transitional Cell
  • 3211 Oncology and carcinogenesis
  • 1117 Public Health and Health Services
 

Citation

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Talukder, R., Makrakis, D., Lin, G. I., Diamantopoulos, L. N., Dawsey, S., Gupta, S., … Khaki, A. R. (2022). Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma. Clin Genitourin Cancer, 20(6), 558–567. https://doi.org/10.1016/j.clgc.2022.08.006
Talukder, Rafee, Dimitrios Makrakis, Genevieve Ihsiu Lin, Leonidas N. Diamantopoulos, Scott Dawsey, Shilpa Gupta, Lucia Carril-Ajuria, et al. “Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma.Clin Genitourin Cancer 20, no. 6 (December 2022): 558–67. https://doi.org/10.1016/j.clgc.2022.08.006.
Talukder R, Makrakis D, Lin GI, Diamantopoulos LN, Dawsey S, Gupta S, et al. Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma. Clin Genitourin Cancer. 2022 Dec;20(6):558–67.
Talukder, Rafee, et al. “Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma.Clin Genitourin Cancer, vol. 20, no. 6, Dec. 2022, pp. 558–67. Pubmed, doi:10.1016/j.clgc.2022.08.006.
Talukder R, Makrakis D, Lin GI, Diamantopoulos LN, Dawsey S, Gupta S, Carril-Ajuria L, Castellano D, de Kouchkovsky I, Jindal T, Koshkin VS, Park JJ, Alva A, Bilen MA, Stewart TF, McKay RR, Tripathi N, Agarwal N, Vather-Wu N, Zakharia Y, Morales-Barrera R, Devitt ME, Cortellini A, Fulgenzi CAM, Pinato DJ, Nelson A, Hoimes CJ, Gupta K, Gartrell BA, Sankin A, Tripathi A, Zakopoulou R, Bamias A, Murgic J, Fröbe A, Rodriguez-Vida A, Drakaki A, Liu S, Lu E, Kumar V, Lorenzo GD, Joshi M, Isaacsson-Velho P, Buznego LA, Duran I, Moses M, Barata P, Sonpavde G, Wright JL, Yu EY, Montgomery RB, Hsieh AC, Grivas P, Khaki AR. Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma. Clin Genitourin Cancer. 2022 Dec;20(6):558–567.
Journal cover image

Published In

Clin Genitourin Cancer

DOI

EISSN

1938-0682

Publication Date

December 2022

Volume

20

Issue

6

Start / End Page

558 / 567

Location

United States

Related Subject Headings

  • Urinary Bladder Neoplasms
  • Treatment Outcome
  • Retrospective Studies
  • Oncology & Carcinogenesis
  • Immune Checkpoint Inhibitors
  • Humans
  • Cohort Studies
  • Carcinoma, Transitional Cell
  • 3211 Oncology and carcinogenesis
  • 1117 Public Health and Health Services