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Pazopanib as a possible option for the treatment of metastatic non-clear cell renal carcinoma patients: a systematic review.

ABSTRACT: Background:Effective systemic treatment of non-clear cell renal carcinoma (nccRCC) is still an unmet clinical need, with few studies to support an evidence-based approach. To date, the only recommended standard first-line treatment is sunitinib. Pazopanib may also be used in nccRCC but its place in therapy is not clearly established. It has comparable efficacy and better tolerability than sunitinib in clear cell renal carcinoma. Our objective was to review the use of pazopanib in metastatic nccRCC. Methods:We conducted a systematic review according to PRISMA guidelines. Any type of study reporting the use of pazopanib in metastatic renal cell carcinoma including cases with non-clear cell histology was eligible. Results:In all, 15 studies were included in our analysis, including a total of 318 nccRCC patients treated with pazopanib. Most studies were retrospective (n?=?12); three were prospective trials. The specific outcomes of nccRCC patients were reported by four studies. Pazopanib alone as first-line treatment gave overall response rates ranging from 27% to 33%, disease control rates of 81-89%, median progression free survival of 8.1-16.5?months and median overall survival of 17.3-31.0?months. Grade 3-4 adverse events rates were 21-55%. Conclusion:The present review provides for the first time a systematic summary of evidence about the possible use of pazopanib as first-line treatment for nccRCC, with a favorable outcome despite the low strength of evidence. Pazopanib could be considered as a possible therapeutic option in this setting.

SUBMITTER: Bersanelli M

PROVIDER: S-EPMC7278098 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Pazopanib as a possible option for the treatment of metastatic non-clear cell renal carcinoma patients: a systematic review.

Bersanelli Melissa M Brunelli Matteo M Gnetti Letizia L Maestroni Umberto U Buti Sebastiano S

Therapeutic advances in medical oncology 20200526

<h4>Background</h4>Effective systemic treatment of non-clear cell renal carcinoma (nccRCC) is still an unmet clinical need, with few studies to support an evidence-based approach. To date, the only recommended standard first-line treatment is sunitinib. Pazopanib may also be used in nccRCC but its place in therapy is not clearly established. It has comparable efficacy and better tolerability than sunitinib in clear cell renal carcinoma. Our objective was to review the use of pazopanib in metasta ...[more]

PMID: 32550862

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Project description:BackgroundClear cell renal cell carcinoma (ccRCC) is the most common subtype among renal cancer and is associated with poor prognosis if metastasized. Up to one third of patients with local disease at diagnosis will develop metastasis after nephrectomy, and there is a need for new molecular markers to identify patients with high risk of tumor progression. In the present study, we performed genome-wide promoter DNA methylation analysis at diagnosis to identify DNA methylation profiles associated with risk for progress.MethodDiagnostic tissue samples from 115 ccRCC patients were analysed by Illumina HumanMethylation450K arrays and methylation status of 155,931 promoter associated CpGs were related to genetic aberrations, gene expression and clinicopathological parameters.ResultsThe ccRCC samples separated into two clusters (cluster A/B) based on genome-wide promoter methylation status. The samples in these clusters differed in tumor diameter (p < 0.001), TNM stage (p < 0.001), morphological grade (p < 0.001), and patients outcome (5 year cancer specific survival (pCSS5yr) p < 0.001 and cumulative incidence of progress (pCIP5yr) p < 0.001. An integrated genomic and epigenomic analysis in the ccRCCs, revealed significant correlations between the total number of genetic aberrations and total number of hypermethylated CpGs (R = 0.435, p < 0.001), and predicted mitotic age (R = 0.407, p < 0.001). We identified a promoter methylation classifier (PMC) panel consisting of 172 differently methylated CpGs accompanying progress of disease. Classifying non-metastatic patients using the PMC panel showed that PMC high tumors had a worse prognosis compared with the PMC low tumors (pCIP5yr 38% vs. 8%, p = 0.001), which was confirmed in non-metastatic ccRCCs in the publically available TCGA-KIRC dataset (pCIP5yr 39% vs. 16%, p < 0.001).ConclusionDNA methylation analysis at diagnosis in ccRCC has the potential to improve outcome-prediction in non-metastatic patients at diagnosis.

Dataset Information

Pazopanib as a possible option for the treatment of metastatic non-clear cell renal carcinoma patients: a systematic review.

Publications

Pazopanib as a possible option for the treatment of metastatic non-clear cell renal carcinoma patients: a systematic review.

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