Dataset Information

Evaluation of immunotherapy and targeted therapy treatment on renal cell carcinoma: A Bayesian network analysis.

ABSTRACT: Clinical trials have previously assessed various therapies for renal cell carcinoma (RCC); however, there is currently a lack of direct comparisons between these therapies. The present study identified published studies on RCC through Web of Science, PubMed, EMBASE, Cochrane Library of Controlled Trials and Clinical trials.gov that were written in the English language and published by February 2019. The data were selected and extracted independently by two reviewers. Standard pair-wise meta-analyses were performed using Stata. Network meta-analyses were subsequently performed using WinBUGS (version 1.4.3). The primary outcome of the present study was progression-free survival (PFS). Secondary outcomes included overall survival (OS), objective response rate (ORR) and adverse events of various targeted therapies. The results were presented as cumulative odds ratio, hazard ratio, corresponding 95% confidence interval and the surface under the cumulative ranking curve, which was used to rank the probabilities and outcome of each treatment in RCC. A total of 31 eligible publications for 18 randomized controlled trials consisting of 11,498 participants were included in the present study. The network meta-analyses revealed that a combination of lenvantinib and everolimus ranked first out of 16 treatments in terms of PFS, OS and ORR (probability of 54.0, 53.4 and 61.0%, respectively).

SUBMITTER: Wei W

PROVIDER: S-EPMC6924115 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Evaluation of immunotherapy and targeted therapy treatment on renal cell carcinoma: A Bayesian network analysis.

Wei Wei W Peng Ruihao R Kuang Lishan L Xu Changyuan C Cao Yan Y Zeng Luqing L Wen Ximei X Qin Qianqian Q Zheng Cuncai C Li Wenyun W Xia Sujian S

Oncology letters 20191114 1

Clinical trials have previously assessed various therapies for renal cell carcinoma (RCC); however, there is currently a lack of direct comparisons between these therapies. The present study identified published studies on RCC through Web of Science, PubMed, EMBASE, Cochrane Library of Controlled Trials and Clinical trials.gov that were written in the English language and published by February 2019. The data were selected and extracted independently by two reviewers. Standard pair-wise meta-anal ...[more]

PMID: 31897138

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Project description:ImportanceClinical trials have shown an overall survival (OS) benefit associated with first-line immunotherapy (IT) and combination targeted therapy (TT) and IT regimens compared with TT among patients with metastatic clear cell renal cell carcinoma (RCC). Generalizability of these findings in a real-world cohort outside of a clinical trial setting is unclear.ObjectiveTo assess the association of first-line TT, IT, and combination TT and IT regimens with OS in a real-world cohort of patients with metastatic clear cell RCC.Design, setting, and participantsThis retrospective propensity-matched cohort study identified 5872 patients with metastatic clear cell RCC in the National Cancer Database from January 1, 2015, to December 31, 2017, who received first-line TT, IT, or combination TT and IT and were not treated on a clinical trial protocol. Patients were stratified by first-line systemic treatment. Statistical analysis was conducted from October 1 to December 1, 2020.Main outcomes and measuresThe primary outcome was OS from the date of diagnosis to death or censoring at last follow-up. After 1:1:1 nearest-neighbor caliper matching of propensity scores, survival analyses were conducted using Cox proportional hazards regression and Kaplan-Meier estimates.ResultsThe final study population included 5872 patients (TT group: n = 4755 [81%]; 3332 men [70%]; median age, 64 years [interquartile range, 57-71 years]; IT group: n = 638 [11%]; 475 men [74%]; median age, 61 years [interquartile range, 54-69 years]; and combination TT and IT group: n = 479 [8%]; 321 men [67%]; median age, 62 years [interquartile range, 55-69 years]), and the matched cohort included 1437 patients (479 per treatment group). Patients in the IT and combination TT and IT groups were younger than those in the TT group, had fewer comorbid conditions (Charlson-Deyo score of 0, 480 of 638 [75%] in the TT group, 356 of 479 [74%] in the IT group, and 3273 of 4755 [69%] in the combination TT and IT group), and were more often treated at academic centers (315 of 638 [49%], 216 of 479 [45%], and 1935 of 4755 [41%], respectively). Both first-line IT and combination TT and IT were associated with improved OS compared with first-line TT for patients with metastatic clear cell RCC (IT group: hazard ratio [HR], 0.60 [95% CI, 0.48-0.75]; P < .001; combination TT and IT group: HR, 0.74 [95% CI, 0.60-0.91]; P = .005). No survival difference was seen between the IT and combination TT and IT groups (combination TT and IT: HR, 1.24 [95% CI, 0.98-1.56]; P = .08).Conclusions and relevanceThis study suggests that both first-line IT and combination TT and IT were associated with improved OS compared with first-line TT for patients with metastatic clear cell RCC. These findings are similar to those identified in recently reported clinical trials, lending confidence to the broader applicability of these findings outside of a clinical trial setting.

Project description:Ubiquitin modification is the most common protein post-translational modification (PTM) process in organisms, and 1332 ubiquitin regulators have been identified in humans. Ubiquitin regulators, especially E3 ligases and deubiquitinases, are widely involved in immune processes. This study aims to explore the ubiquitin modification features of clear cell renal cell carcinoma (ccRCC) and to elucidate the role of such ubiquitin modifications in shaping anti-tumor immunity and individual benefits from immune checkpoint blockade (ICB). A comprehensive analysis was performed in the TCGA cohort (n = 530) and GEO cohort (n = 682). RNA sequencing data of 758 differentially expressed regulators, which was validated by the proteomics data, was used for k-means unsupervised consensus clustering and three ubiquitin patterns of ccRCC were identified. Then, we focused on the ubiquitin modification and tumor progression signatures, immune infiltration characteristics, and prognostic value. The three patterns with different ubiquitin modification signatures correspond to "immune desert phenotype," "immune resistance phenotype," and "immune-inflammatory phenotype," respectively. To facilitate clinical application, we constructed a ubiquitin score to evaluate individual patients' ubiquitination outcome, and it was demonstrated to be an independent risk factor for overall survival (OS) in multivariate Cox analysis. It was found that the high score group was correlated to higher immune cells infiltrating level and PD-1/PD-L1/CTLA-4 expression. More importantly, we found that the high score group was predicted to be sensitive to anti-PD-1 treatment, while the low-score group showed lower predicted IC50 values in treatment with Pazopanib and Axitinib. In summary, this study elucidated the potential link between ubiquitin modification and immune infiltration landscape of ccRCC for the first time and provided a new assessment protocol for the precise selection of treatment strategies for patients with advanced ccRCC.

Dataset Information

Evaluation of immunotherapy and targeted therapy treatment on renal cell carcinoma: A Bayesian network analysis.

Publications

Evaluation of immunotherapy and targeted therapy treatment on renal cell carcinoma: A Bayesian network analysis.

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