A Living, Interactive Systematic Review and Network Meta-analysis of First-line Treatment of Metastatic Renal Cell Carcinoma

Riaz, Irbaz Bin; He, Huan; Ryu, Alexander J.; Siddiqi, Rabbia; Naqvi, Syed Arsalan Ahmed; Yao, Yuan; Husnain, Muhammad; Narasimhulu, Deepa Maheswari; Mathew, Jessey; Sipra, Qurat Ul Ain Riaz; Vandvik, Per Olav; Joseph, Richard W.; Liu, Hongfang; Wang, Zhen; Herasevich, Vitaly; Singh, Parminder; Hussain, Syed A.; Ho, Thai H.; Bryce, Alan H.; Pagliaro, Lance C.; Murad, Mohammad Hassan; Costello, Brian A.

doi:10.1016/j.eururo.2021.03.016

Cited by 50 publications

(42 citation statements)

References 53 publications

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“…[13][14][15][16][17] However, the incidences of discontinuation of both combined agents due to AEs and the proportion of patients receiving high-dose glucocorticoids for the management of irAEs in ipilimumab plus nivolumab were much higher than those in combined therapies with an IO drug plus TKI. [13][14][15][16][17] In recent years, there have been several studies comparing clinical efficacies of IO drug-based combination therapies by network meta-analysis, [30][31][32][33][34][35][36] which makes it possible to provide rankings with statistical adjustments, despite the presence of bias associated with cross comparisons of multiple trials. Although differing in details, these studies mostly demonstrated that combined therapy with IO drugs and TKIs provide oncological outcomes superior to ipilimumab plus nivolumab.…”

Section: Comparisons Among Io Drug-based Combination Therapiesmentioning

confidence: 99%

Comprehensive assessments of immuno‐oncology drug‐based combination therapies as first‐line treatment for advanced renal cell carcinoma

et al. 2022

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Over the last decade, there have been substantial progress in the field of systemic therapy for advanced renal cell carcinoma. Through the transition from treatment with cytokines to molecular-targeted agents, and currently to immunooncology drugs, the prognostic outcomes of patients with advanced renal cell carcinoma have been markedly improved. In particular, based on the promising outcomes of recently conducted pivotal randomized clinical trials, immuno-oncology drug-based combination therapy by either dual immune checkpoint inhibition or combined inhibition of an immune checkpoint and tyrosine kinase, is currently regarded as a standard of care for treatment-na€ ıve advanced renal cell carcinoma patients. However, insufficient data are available with respect to the selection of optimal systemic therapies for advanced renal cell carcinoma in the first-line setting due to the lack of a head-to-head comparison between approved immuno-oncology drug-based combination therapies. In this review, therefore, we summarize interesting findings associated with first-line combination therapies for advanced renal cell carcinoma obtained from both randomized clinical trials and real-world clinical practices, in order to present useful guidance to help make treatment decisions for patients with treatment-na€ ıve advanced renal cell carcinoma.

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Section: Comparisons Among Io Drug-based Combination Therapiesmentioning

confidence: 99%

Comprehensive assessments of immuno‐oncology drug‐based combination therapies as first‐line treatment for advanced renal cell carcinoma

et al. 2022

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“…As for the local advanced or distant metastatic renal cancer, chemotherapy is still recognized as the most ideal treatment therapy. 13 With technological development, from inhibitor of vascular endothelial growth factor (VEGF) to tyrosine kinase inhibitor (TKI), several molecules have been demonstrated to have successful therapeutic effects. Recently, immune checkpoint inhibitor (ICI) have gradually shown efficacy and safety in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

“…To date, the standard treatment of renal cancer cases is surgery with continuous follow‐up. As for the local advanced or distant metastatic renal cancer, chemotherapy is still recognized as the most ideal treatment therapy 13 . With technological development, from inhibitor of vascular endothelial growth factor (VEGF) to tyrosine kinase inhibitor (TKI), several molecules have been demonstrated to have successful therapeutic effects.…”

Section: Introductionmentioning

confidence: 99%

LncRNA SNHG1 promotes renal cell carcinoma progression through regulation of HMGA2 via sponging miR‐103a

Gui

Wang

et al. 2022

Clinical Laboratory Analysis

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Background Long noncoding RNAs (LncRNAs) plays a vital role in tumorigenesis and development. The molecular mechanism of SNHG1 in renal cell carcinoma (RCC) has not been illustrated. The aim of this research was to explore the expression and function of LncRNA SNHG1 in RCC. Material and Methods The expression of SNHG1 in clinical tissues and RCC cell lines was detected. Luciferase reporter assay was performed to verify the correlation between SNHG1, miR‐103a, and HMGA2. CCK‐8 assay was performed to examine cell viability. Cell apoptosis was analyzed using flow cytometry. Cell invasion capacity was determined by Transwell assays. The protein level of HMGA2 was analyzed by Western blotting. Results The expression of SNHG1 markedly increased in RCC tissues and cell lines. Subsequent studies identified SNHG1 as a miRNA sponge for miR‐103a. In addition, SNHG1 knockdown and miR‐103a overexpression significantly inhibited progression of RCC. miR‐103a also regulated HMGA2 levels. Conclusion Our findings showed that SNHG1 was upregulated in RCC cells and tissues. SNHG1 promoted the malignant characteristics of RCC cells. Its regulatory effect may be regulation of HMGA2 by sponging miR‐103a. Therefore, Our study facilitates the understanding of SNHG1 function in RCC.

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“…First‐line treatment of metastatic renal cell carcinoma (mRCC) has changed substantially in recent years because of the introduction of a new therapy regimen, mainly based on immune checkpoint inhibition (IO) 1–3 . Currently, two different types of approved first‐line combination therapies are applied equivalently for the treatment of intermediate and poor‐risk metastatic mRCC according to IMDC (International Metastatic Renal Cell Carcinoma Database Consortium Score): (1) a combination of αPD‐1 and αCTLA‐4 immune checkpoint inhibitors as well as (2) a combination of αPD‐1 (or αPD‐L1) with small‐molecule tyrosine kinase inhibitors (TKI) targeting the vascular endothelial growth factor receptor (VEGFR) 4–8 .…”

Section: Introductionmentioning

confidence: 99%

C‐reactive protein flare‐response predicts long‐term efficacy to first‐line anti‐PD‐1‐based combination therapy in metastatic renal cell carcinoma

Klümper

Schmucker

Hahn³

et al. 2021

Clin & Trans Imm

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Objectives Immune checkpoint blockade (IO) has revolutionised the treatment of metastatic renal cell carcinoma (mRCC). Early C‐reactive protein (CRP) kinetics, especially the recently introduced CRP flare‐response phenomenon, has shown promising results to predict IO efficacy in mRCC, but has only been studied in second line or later. Here, we aimed to validate the predictive value of early CRP kinetics for 1st‐line treatment of mRCC with αPD‐1 plus either αCTLA‐4 (IO+IO) or tyrosine kinase inhibitor (IO+TKI). Methods In this multicentre retrospective study, we investigated the predictive potential of early CRP kinetics during 1st‐line IO therapy. Ninety‐five patients with mRCC from six tertiary referral centres with either IO+IO (N = 59) or IO+TKI (N = 36) were included. Patients were classified as CRP flare‐responders, CRP responders or non‐CRP responders as previously described, and their oncological outcome was compared. Results Our data validate the predictive potential of early CRP kinetics in 1st‐line immunotherapy in mRCC. CRP responders, especially CRP flare‐responders, had significantly prolonged progression‐free survival (PFS) compared with non‐CRP responders (median PFS: CRP flare‐responder: 19.2 months vs. responders: 16.2 vs. non‐CRP responders: 5.6, P < 0.001). In both the IO+IO and IO+TKI subgroups, early CRP kinetics remained significantly associated with improved PFS. CRP flare‐response was also associated with long‐term response ≥ 12 months. Conclusions Early CRP kinetics appears to be a low‐cost and easy‐to‐implement on‐treatment biomarker to predict response to 1st‐line IO combination therapy. It has potential to optimise therapy monitoring and might represent a new standard of care biomarker for immunotherapy in mRCC.

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A Living, Interactive Systematic Review and Network Meta-analysis of First-line Treatment of Metastatic Renal Cell Carcinoma

Cited by 50 publications

References 53 publications

Comprehensive assessments of immuno‐oncology drug‐based combination therapies as first‐line treatment for advanced renal cell carcinoma

Comprehensive assessments of immuno‐oncology drug‐based combination therapies as first‐line treatment for advanced renal cell carcinoma

LncRNA SNHG1 promotes renal cell carcinoma progression through regulation of HMGA2 via sponging miR‐103a

C‐reactive protein flare‐response predicts long‐term efficacy to first‐line anti‐PD‐1‐based combination therapy in metastatic renal cell carcinoma

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