Logo image
Safety and efficacy of immune checkpoint inhibitors in advanced urological cancers with pre-existing autoimmune disorders: a retrospective international multicenter study
Journal article   Open access   Peer reviewed

Safety and efficacy of immune checkpoint inhibitors in advanced urological cancers with pre-existing autoimmune disorders: a retrospective international multicenter study

Nieves Martinez Chanza, Wanling Xie, Majd Issa, Hannah Dzimitrowicz, Abhishek Tripathi, Benoit Beuselinck, Elaine Lam, Yousef Zakharia, Rana Mckay, Sumit Shah, …
Journal for immunotherapy of cancer, Vol.8(1), p.e000538
03/2020
DOI: 10.1136/jitc-2020-000538
PMCID: PMC7174076
PMID: 32217762
url
https://doi.org/10.1136/jitc-2020-000538View
Published (Version of record) Open Access

Abstract

BackgroundThere is limited experience regarding the safety and efficacy of checkpoint inhibitors (CPI) in patients with autoimmune disorders (AD) and advanced urological cancers as they are generally excluded from clinical trials due to risk of exacerbations.MethodsThis multicenter retrospective cohort analysis of patients with advanced renal cell cancer (RCC) and urothelial cancer (UC) with pre-existing AD treated with CPI catalogued the incidence of AD exacerbations, new immune-related adverse events (irAEs) and clinical outcomes. Competing risk models estimated cumulative incidences of exacerbations and new irAEs at 3 and 6 months.ResultsOf 106 patients with AD (58 RCC, 48 UC) from 10 centers, 35 (33%) had grade 1/2 clinically active AD of whom 10 (9%) required corticosteroids or immunomodulators at baseline. Exacerbations of pre-existing AD occurred in 38 (36%) patients with 17 (45%) requiring corticosteroids and 6 (16%) discontinuing CPI. New onset irAEs occurred in 40 (38%) patients with 22 (55%) requiring corticosteroids and 8 (20%) discontinuing CPI. Grade 3/4 events occurred in 6 (16%) of exacerbations and 13 (33%) of new irAEs. No treatment-related deaths occurred. Median follow-up was 15 months. For RCC, objective response rate (ORR) was 31% (95% CI 20% to 45%), median time to treatment failure (TTF) was 7 months (95% CI 4 to 10) and 12-month overall survival (OS) was 78% (95% CI 63% to 87%). For UC, ORR was 40% (95% CI 26% to 55%), median TTF was 5.0 months (95% CI 2.3 to 9.0) and 12-month OS was 63% (95% CI 47% to 76%).ConclusionsPatients with RCC and UC with well-controlled AD can benefit from CPI with manageable toxicities that are consistent with what is expected of a non-AD population. Prospective study is warranted to comprehensively evaluate the benefits and safety of CPI in patients with AD.

Details

Logo image