Journal article
Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma
Clinical genitourinary cancer, Vol.20(6), pp.558-567
12/01/2022
DOI: 10.1016/j.clgc.2022.08.006
PMCID: PMC10233855
PMID: 36155169
Abstract
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.
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.
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.
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.
Immune checkpoint inhibitors improve overall survival in advanced urothelial carcinoma, but response rates remain modest. We performed a multi-institutional retrospective cohort study comparing outcomes (observed response rate, progression-free, and overall survival) between patients based on time from initiation of first line platinum-based chemotherapy to second line immune checkpoint inhibitor. This study provides preliminary data that earlier resistance to platinum-based chemotherapy may be associated with shorter survival in those who receive subsequent ICI.
Details
- Title: Subtitle
- Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma
- Creators
- Rafee Talukder - University of WashingtonDimitrios Makrakis - University of WashingtonGenevieve Ihsiu Lin - University of WashingtonLeonidas N. Diamantopoulos - University of PittsburghScott Dawsey - Cleveland ClinicShilpa Gupta - Cleveland ClinicLucia Carril-Ajuria - Department of Medical Oncology, Hospital Universitario, Madrid, SpainDaniel Castellano - Department of Medical Oncology, Hospital Universitario, Madrid, SpainIvan de Kouchkovsky - University of California, San FranciscoTanya Jindal - University of California, San FranciscoVadim S. Koshkin - University of California, San FranciscoJoseph J. Park - University of MichiganAjjai Alva - University of MichiganMehmet A. Bilen - Emory UniversityTyler F. Stewart - University of California San DiegoRana R. McKay - University of California San DiegoNishita Tripathi - University of UtahNeeraj Agarwal - University of UtahNaomi Vather-Wu - Department of Medicine, University of Iowa, Iowa City, IAYousef Zakharia - University of IowaRafael Morales-Barrera - Hebron UniversityMichael E. Devitt - University of VirginiaAlessio Cortellini - Imperial College LondonClaudia Angela Maria Fulgenzi - Imperial College LondonDavid J. Pinato - Imperial College LondonAriel Nelson - Medical College of WisconsinChristopher J. Hoimes - Case Western Reserve UniversityKavita Gupta - Montefiore Medical CenterBenjamin A. Gartrell - Montefiore Medical CenterAlex Sankin - Montefiore Medical CenterAbhishek Tripathi - University of Oklahoma Health Sciences CenterRoubini Zakopoulou - National and Kapodistrian University of AthensAristotelis Bamias - National and Kapodistrian University of AthensJure Murgic - Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, ZagrebAna Fröbe - Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, ZagrebAlejo Rodriguez-Vida - Hospital Del MarAlexandra Drakaki - David Geffen School of Medicine at UCLASandy Liu - David Geffen School of Medicine at UCLAEric Lu - David Geffen School of Medicine at UCLAVivek Kumar - Brigham and Women's HospitalGiuseppe Di Lorenzo - University of MoliseMonika Joshi - Pennsylvania State UniversityPedro Isaacsson-Velho - Sidney Kimmel Comprehensive Cancer CenterLucia Alonso Buznego - Marqués de Valdecilla University HospitalIgnacio Duran - Marqués de Valdecilla University HospitalMarcus Moses - University of New OrleansPedro Barata - University of New OrleansGuru Sonpavde - Dana-Farber Cancer InstituteJonathan L. Wright - Fred Hutchinson Cancer Center, Seattle, WAEvan Y. Yu - University of WashingtonRobert Bruce Montgomery - University of WashingtonAndrew C. Hsieh - University of WashingtonPetros Grivas - University of WashingtonAli Raza Khaki - Stanford University
- Resource Type
- Journal article
- Publication Details
- Clinical genitourinary cancer, Vol.20(6), pp.558-567
- DOI
- 10.1016/j.clgc.2022.08.006
- PMID
- 36155169
- PMCID
- PMC10233855
- NLM abbreviation
- Clin Genitourin Cancer
- ISSN
- 1558-7673
- eISSN
- 1938-0682
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 12/01/2022
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984544939102771
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