Treatment Rechallenge With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

Dimitrios Makrakis; Dimitra Rafailia Bakaloudi; Rafee Talukder; Genevieve Ihsiu Lin; Leonidas N. Diamantopoulos; Tanya Jindal; Naomi Vather-Wu; Yousef Zakharia; Nishita Tripathi; Neeraj Agarwal; Scott Dawsey; Shilpa Gupta; Eric Lu; Alexandra Drakaki; Sandy Liu; Roubini Zakopoulou; Aristotelis Bamias; Claudia-Maria Fulgenzi; Alessio Cortellini; David Pinato; Pedro Barata; Petros Grivas; Ali Raza Khaki; Vadim S. Koshkin

doi:10.1016/j.clgc.2022.11.003

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Treatment Rechallenge With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

Journal article

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Peer reviewed

Treatment Rechallenge With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

Dimitrios Makrakis, Dimitra Rafailia Bakaloudi, Rafee Talukder, Genevieve Ihsiu Lin, Leonidas N. Diamantopoulos, Tanya Jindal, Naomi Vather-Wu, Yousef Zakharia, Nishita Tripathi, Neeraj Agarwal, …

Clinical genitourinary cancer, Vol.21(2), pp.286-294

04/2023

DOI: 10.1016/j.clgc.2022.11.003

PMID: 36481176

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Abstract

•Patients with advanced urothelial cancer (aUC) rechallenged with an ICI-based regimen may achieve disease control.•Rechallenge with ICI-based therapy in aUC seems feasible with manageable toxicity.•Further data are needed to optimally select patients for ICI rechallenge in aUC. To examine patient and disease characteristics, toxicity, and clinical outcomes for patients with advanced urothelial carcinoma (aUC) who are rechallenged with immune checkpoint inhibitor (ICI)-based therapy. In this retrospective cohort, we included patients treated with ICI for aUC after having prior ICI treatment. Endpoints included the evaluation of radiographic response and disease control rates with first and second ICI courses, outcomes based on whether there was a change in ICI class (anti-PD-1 vs. anti-PD-L1), and assessment of the reasons for ICI discontinuation. We identified 25 patients with aUC from 9 institutions who received 2 separate ICI courses. ORR with first ICI and second ICI were 39% and 13%, respectively. Most patients discontinued first ICI due to progression (n = 19) or treatment-related toxicity (n = 4). Thirteen patients received non-ICI treatment between the first and second ICI, and 12 patients changed ICI class (anti-PD-1 vs. anti-PD-L1) at rechallenge. Among 10 patients who changed ICI class, 8 (80%) had progressive disease as best response with second ICI, while among 12 patients re-treated with the same ICI class, only 3 (25%) had progressive disease as best response at the time of rechallenge. With second ICI, most patients discontinued treatment due to progression (n = 18) or patient preference (n = 2). A proportion of patients with aUC rechallenged with ICI-based regimens may achieve disease control, supporting clinical trials in that setting, especially with ICI-based combinations. Future studies are needed to validate our results and should also focus on identifying biomarkers predictive of benefit with ICI rechallenge. Immune checkpoint inhibitors (ICI) improve outcomes in patients with advanced urothelial carcinoma (aUC). However, most patients may not respond and develop progressive disease, while toxicity can be an issue. ICI therapy remains a questionable consideration for rechallenge after other therapies are used. Our study described characteristics and treatment response in patients with aUC who were rechallenged with an ICI-based regimen.

Bladder cancer

Immunotherapy

Urinary tract cancer

urothelial cancer

Details

Title: Subtitle: Treatment Rechallenge With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma
Creators: Dimitrios Makrakis - University of Washington
Dimitra Rafailia Bakaloudi - University of Washington
Rafee Talukder - University of Washington
Genevieve Ihsiu Lin - University of Washington
Leonidas N. Diamantopoulos - University of Pittsburgh
Tanya Jindal - University of California, San Francisco
Naomi Vather-Wu - Department of Medicine, University of Iowa, Iowa City, IA
Yousef Zakharia - University of Iowa
Nishita Tripathi - University of Utah
Neeraj Agarwal - University of Utah
Scott Dawsey - Cleveland Clinic
Shilpa Gupta - Cleveland Clinic
Eric Lu - David Geffen School of Medicine at UCLA
Alexandra Drakaki - David Geffen School of Medicine at UCLA
Sandy Liu - David Geffen School of Medicine at UCLA
Roubini Zakopoulou - National and Kapodistrian University of Athens
Aristotelis Bamias - National and Kapodistrian University of Athens
Claudia-Maria Fulgenzi - Imperial College London
Alessio Cortellini - Imperial College London
David Pinato - Imperial College London
Pedro Barata - Tulane Medical School, New Orleans, LA
Petros Grivas - University of Washington
Ali Raza Khaki - Stanford University
Vadim S. Koshkin - University of California, San Francisco
Resource Type: Journal article
Publication Details: Clinical genitourinary cancer, Vol.21(2), pp.286-294
DOI: 10.1016/j.clgc.2022.11.003
PMID: 36481176
NLM abbreviation: Clin Genitourin Cancer
ISSN: 1558-7673
eISSN: 1938-0682
Publisher: Elsevier Inc
Language: English
Date published: 04/2023
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984544624202771

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