Dataset Information

Novel risk group stratification for metastatic urothelial cancer patients treated with immune checkpoint inhibitors.

ABSTRACT:

Background

We developed a novel risk scoring system for urothelial cancer (UC) patients receiving immune checkpoint inhibitors (ICI).

Methods

We conducted a retrospective review of 67 UC patients treated with ICI at Winship Cancer Institute of Emory University from 2015 to 2018. Using stepwise variable selection in Cox proportional hazard model and Sullivan's weighting schema, baseline platelet-to-lymphocyte ratio (PLR), presence of liver metastasis, baseline albumin, and baseline Eastern Cooperative Oncology Group performance status (ECOG PS) were used for risk scoring. Patients were categorized into good risk (risk score 0-1), intermediate risk (risk score 2-3), and poor risk (risk score 4-6). Univariable (UVA) and multivariable analysis (MVA) and Kaplan-Meier method were used to assess overall survival (OS) and progression free survival (PFS).

Results

The Emory Risk Scoring System had C-statistics of 0.74 (Standard Error = 0.047) in predicting OS and 0.70 (Standard Error = 0.043) in predicting PFS. Compared to good risk patients, poor risk patients had significantly shorter OS and PFS in both UVA and MVA (all P < .001), and intermediate risk patients had significantly shorter OS and PFS in both UVA and MVA (all P < .03).

Conclusions

Risk scoring using baseline PLR, presence of liver metastasis, baseline albumin, and baseline ECOG PS may effectively predict OS and PFS in UC patients receiving ICI.

SUBMITTER: Shabto JM

PROVIDER: S-EPMC7163104 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

Novel risk group stratification for metastatic urothelial cancer patients treated with immune checkpoint inhibitors.

Shabto Julie M JM Martini Dylan J DJ Liu Yuan Y Ravindranathan Deepak D Brown Jacqueline J Hitron Emilie E EE Russler Greta A GA Caulfield Sarah S Kissick Haydn H Alemozaffar Mehrdad M Ogan Kenneth K Harris Wayne B WB Master Viraj A VA Kucuk Omer O Carthon Bradley C BC Bilen Mehmet A MA

Cancer medicine 20200225 8

<h4>Background</h4>We developed a novel risk scoring system for urothelial cancer (UC) patients receiving immune checkpoint inhibitors (ICI).<h4>Methods</h4>We conducted a retrospective review of 67 UC patients treated with ICI at Winship Cancer Institute of Emory University from 2015 to 2018. Using stepwise variable selection in Cox proportional hazard model and Sullivan's weighting schema, baseline platelet-to-lymphocyte ratio (PLR), presence of liver metastasis, baseline albumin, and baseline ...[more]

PMID: 32100417

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Project description:BackgroundThe International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria are the gold standard for risk-stratifying patients with metastatic renal cell cancer (mRCC). We developed a novel risk scoring system for patients with mRCC treated with immune checkpoint inhibitors (ICIs).MethodsWe performed a retrospective analysis of 100 ICI-treated patients with mRCC at Winship Cancer Institute from 2015 to 2018. Several baseline variables were collected, including markers of inflammation, body mass index (BMI), and sites of metastatic disease, and all were considered for inclusion in our risk scoring system. Upon variable selection in multivariable model, monocyte-to-lymphocyte ratio (MLR), BMI, and number and sites of metastases at baseline were used for risk score calculation. Patients were categorized using four-level risk groups as good (risk score = 0), intermediate (risk score = 1), poor (risk score = 2), or very poor (risk score = 3-4). Cox's proportional hazard model and the Kaplan-Meier method were implemented for survival outcomes.ResultsMost patients were male (66%) with clear cell renal cell carcinoma (72%). The majority (71%) received anti-programmed cell death protein-1 monotherapy. Our risk scoring criteria had higher Uno's concordance statistics than IMDC in predicting overall survival (OS; 0.71 vs. 0.57) and progression-free survival (0.61 vs. 0.58). Setting good risk (MLR <0.93, BMI ≥24, and D_Met = 0) as the reference, the OS hazard ratios were 29.5 (95% confidence interval [CI], 3.64-238.9), 6.58 (95% CI, 0.84-51.68), and 3.75 (95% CI, 0.49-28.57) for very poor, poor, and intermediate risk groups, respectively.ConclusionRisk scoring using MLR, BMI, and number and sites of metastases may be an effective way to predict survival in patients with mRCC receiving ICI. These results should be validated in a larger, prospective study.Implications for practiceA risk scoring system was created for patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. The results of this study have significant implications for practicing oncologists in the community and academic setting. Importantly, these results identify readily available risk factors that can be used clinically to risk-stratify patients with metastatic renal cell carcinoma who are treated with immune checkpoint inhibitors.

Project description:Most patients with advanced or metastatic urothelial carcinoma do not benefit significantly from Immune checkpoint inhibitors (ICIs) use. A systematic review and meta-analysis of randomized controlled trials to assess the efficacy and activity of ICIs, in terms of Overall Survival (OS), Progression-free survival (PFS), and Objective Response Rate (ORR). We systematically searched for articles from PubMed, Cochrane Library, Embase, and Web of science from their inception to December 1, 2020 with no language restrictions. The search was performed to identify all clinical trials (phase I, phase II, phase III) of ICIs for treating urothelial carcinoma. The endpoints of the meta-analysis were OS, PFS, and ORR, compared unselected patients and in the subgroup of patients characterized by high expression of PD-L1 (PD-L1 selected patients). Sixteen studies comprising 5559 patients were identified, of which data for OS comparison were available from 4 RCTs (2342 patients), two studies for PFS (649 patients), and four RCTs were eligible for ORR analysis (2921 patients). Both pembrolizumab and atezolizumab have showed to improve OS compared to chemotherapy in unselected patients (HR 0.86, 95% CI 0.80-0.93, P = .0001, I2 = 60%), while the difference was not significant in PD-L1 selected patients (HR 0.91, 95% CI 0.77-1.07, P = .23, I2 = 0%). PFS difference was not observed in neither unselected population nor PD-L1 selected patients, the pooled HR of PFS for immunotherapy compared to control treatment was 1.05 (95% CI 0.74-1.49, P = .79, I2 = 85%) and 0.84 (95% CI 0.68-1.03, P = .09, I2 = 0%, respectively. Similar result was observed in ORR, the pooled HR of ORR for immunotherapy compared to control treatment was 1.45 (95% CI 0.53-3.98, P = .47, I2 = 95%) and 2.19 (95% CI 0.79-6.08, P = .13, I2 = 83%), respectively. Immunotherapy could significantly improve survival advantage in unselected patients but not in PD-L1 selected population, indicating that PD-L1 expression may not be a reliable marker in previously platinum-treated patients.

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.

Dataset Information

Novel risk group stratification for metastatic urothelial cancer patients treated with immune checkpoint inhibitors.

Background

Methods

Results

Conclusions

Publications

Novel risk group stratification for metastatic urothelial cancer patients treated with immune checkpoint inhibitors.

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