Dataset Information

Immune-Related Adverse Events and Clinical Outcomes in Advanced Urothelial Cancer Patients Treated With Immune Checkpoint Inhibitors.

ABSTRACT:

Background

In advanced urothelial cancers (UC), immune checkpoint inhibitors (ICI) show promise as a durable therapy. Immune-related adverse events (irAEs), a side effect of ICIs, may serve as an indicator of beneficial response. We investigated the relationship between irAEs and clinical outcomes in patients with advanced UC who received ICI.

Materials and methods

In this retrospective study, we investigated 70 patients with advanced UC treated with ICIs at Winship Cancer Institute from 2015 to 2020. Data on patients were collected through chart review. Cox's proportional hazard model and logistic regression were applied to estimate the association with overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). The possible lead-time bias was handled in extended Cox regression models.

Results

The median age of the cohort was 68. Over one-third (35%) of patients experienced an irAE, with skin being the most frequent organ involved (12.9%). Patients that experienced at least one irAE had significantly enhanced OS (HR: 0.38, 95% CI, 0.18-0.79, P = .009), PFS (HR: 0.27, 95% CI, 0.14-0.53, P < .001), and CB (OR: 4.20, 95% CI, 1.35-13.06, P = .013). Patients who experienced dermatologic irAEs also had significantly greater OS, PFS, and CB.

Conclusion

Of patients with advanced UC that had undergone ICI therapy, those who had irAEs, especially dermatologic irAEs, had significantly greater OS, PFS, and CB. These results may suggest that irAE's may serve as an important marker of durable response to ICI therapy in urothelial cancer. The findings of this study need to be validated with larger cohort studies in the future.

SUBMITTER: Sanda GE

PROVIDER: S-EPMC10712712 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Immune-Related Adverse Events and Clinical Outcomes in Advanced Urothelial Cancer Patients Treated With Immune Checkpoint Inhibitors.

Sanda Gregory E GE Shabto Julie M JM Goyal Subir S Liu Yuan Y Martini Dylan J DJ Nazha Bassel B Brown Jacqueline T JT Yantorni Lauren B LB Anne Russler Greta G Caulfield Sarah S Joshi Shreyas S SS Narayan Vikram M VM Kissick Haydn H Ogan Kenneth K Master Viraj A VA Carthon Bradley C BC Kucuk Omer O Bilen Mehmet Asim MA

The oncologist 20231201 12

<h4>Background</h4>In advanced urothelial cancers (UC), immune checkpoint inhibitors (ICI) show promise as a durable therapy. Immune-related adverse events (irAEs), a side effect of ICIs, may serve as an indicator of beneficial response. We investigated the relationship between irAEs and clinical outcomes in patients with advanced UC who received ICI.<h4>Materials and methods</h4>In this retrospective study, we investigated 70 patients with advanced UC treated with ICIs at Winship Cancer Institu ...[more]

PMID: 37285524

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Project description:ImportanceImmune-related adverse events (irAEs) secondary to immune checkpoint inhibitor (ICI) therapy reportedly improve overall survival (OS) in patients with non-small cell lung cancer (NSCLC). However, studies have been small and the association between irAE severity and OS remains poorly defined.ObjectiveTo examine the association between irAEs and their severity with OS in patients with locally advanced or metastatic NSCLC receiving ICIs.Design, setting, and participantsThis retrospective observational cohort study included patients with NSCLC receiving ICIs between March 1, 2014, and November 30, 2021, with follow-up until March 31, 2023. Data analysis was completed April 26, 2023. The Alberta Immunotherapy Database, a provincial, multicenter cohort, was used to capture data from patients receiving ICIs in Alberta, Canada. Participants included 803 patients 18 years or older who received at least 1 cycle of ICI (alone or with chemotherapy), agnostic to treatment line.ExposureDeveloping an irAE mandating delay or discontinuation of ICI therapy and/or systematic corticosteroids for management of toxic effects (hereinafter referred to as clinically meaningful irAEs).Main outcomes and measuresThe primary outcome was association between irAEs and OS according to Kaplan-Meier analysis. Clinically meaningful irAEs were identified. Patients with poor prognosis (survival <3 months) who may have died prior to irAE development were excluded from OS analysis, mitigating immortal time bias. Adjusted Cox proportional hazards regression analyses ascertained variables associated with OS.ResultsAmong the 803 patients included in the analysis, the median age of patients with irAEs was 69.7 (IQR, 63.1-75.2) years and the median age of those without irAEs was 67.5 (IQR, 60.4-73.3) years, with comparable sex distribution (139 of 295 men [47.1%] and 156 of 295 women [52.9%] with irAEs vs 254 of 505 men [50.3%] and 251 of 505 women [49.7%] without irAEs). Mitigating immortal time bias (n = 611), irAEs were associated with OS (median OS with irAEs, 23.7 [95% CI, 19.3-29.1] months; median OS without irAEs, 9.8 [95% CI, 8.7-11.4] months; P < .001). No OS difference was associated with treatment in hospital vs as outpatients for an irAE (median OS, 20.8 [95% CI, 11.7-30.6] vs 25.6 [95% CI, 20.1-29.8] months; P = .33). Developing irAEs remained associated with OS in the total cohort after Cox proportional hazards regression with known prognostic characteristics (hazard ratio, 0.53 [95% CI, 0.40-0.70]; P < .001).Conclusions and relevanceIn this cohort study of 803 patients with locally advanced or metastatic NSCLC receiving ICIs, developing a clinically meaningful irAE was associated with improved OS. This association was not compromised by hospitalization for severe toxic effects. Whether and how ICI therapy resumption after an irAE is associated with OS warrants further study.

Project description:The present study aimed to evaluate the incidence, characteristics and management of hepatic immune-related adverse events (irAEs) in patients with advanced or metastatic urothelial carcinoma (UC) and renal cell carcinoma (RCC) receiving immune checkpoint inhibitors (ICIs). Data regarding the demographics, ICI regimens and hepatic irAEs from 213 patients with metastatic UC or metastatic RCC receiving ICIs between February 2018 and September 2023 at three tertiary medical centers (Inje University Busan Paik Hospital, Busan, South Korea; Dongnam Institute of Radiological and Medical Sciences Cancer Center, Busan, South Korea; Pusan National University Hospital, Busan, South Korea) in South Korea were collected and retrospectively analyzed. Hepatic irAEs were graded using the Common Terminology Criteria for Adverse Events version 5.0 and classified based on R value patterns. Among the 213 patients evaluated, 76 (35.6%) experienced at least one irAE, whereas 48 (22.5%) developed hepatic irAEs. The median onset time for hepatic irAEs was 6.5 weeks, with incidence rates being higher with combination therapies than with monotherapies (31.8 vs. 18.3%; P=0.014). Furthermore, 72.9 and 27.1% of the patients had grade 1-2 and 3-4 hepatic irAEs, respectively. The patterns of liver toxicity included cholestatic (35.4%), mixed (35.4%) and hepatocellular (29.2%). All patients with grade 1-2 hepatic irAE recovered with supportive treatment without ICI discontinuation or corticosteroids use. Among the 13 patients with grade ≥3 hepatic irAEs, 12 recovered with high-dose corticosteroids, while 1 died due to fulminant hepatitis. Hepatic irAEs are common in patients with advanced and metastatic urologic cancers who are treated with ICIs, particularly with combination therapies. Most cases have low-grade irAE that are manageable without ICI discontinuation; however, severe cases require prompt recognition and treatment with corticosteroids. These findings emphasize the importance of regular liver function monitoring and appropriate management strategies for hepatic irAEs in patients with urologic cancer receiving ICI therapy.

Dataset Information

Immune-Related Adverse Events and Clinical Outcomes in Advanced Urothelial Cancer Patients Treated With Immune Checkpoint Inhibitors.

Background

Materials and methods

Results

Conclusion

Publications

Immune-Related Adverse Events and Clinical Outcomes in Advanced Urothelial Cancer Patients Treated With Immune Checkpoint Inhibitors.

Similar Datasets

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