Comparative effectiveness of first-line immune checkpoint inhibitors plus tyrosine kinase inhibitors according to IMDC risk groups in metastatic renal cell carcinoma: a meta-analysis

Immunotherapy ◽  
2021 ◽  
Author(s):  
Alessandro Rizzo ◽  
Veronica Mollica ◽  
Matteo Santoni ◽  
Matteo Rosellini ◽  
Andrea Marchetti ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Kinase Inhibitors ◽  
Meta Analysis ◽  
Risk Groups ◽  
Risk Patients

Aim: Immune checkpoint inhibitor (ICI)-based combinations have become the new standard of primary systemic treatment for metastatic renal cell carcinoma patients. We performed a meta-analysis aimed at evaluating ICIs plus tyrosine kinase inhibitors (TKIs) combinations across International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups. Materials & methods: All the relevant randomized clinical trials were retrieved through Cochrane library, PubMed/Med and EMBASE; three Phase III randomized clinical trials were included. Results: ICI–TKI combinations significantly decreased the risk of death in IMDC poor- and intermediate-risk patients. Conversely, a nonstatistically significant benefit was observed in favorable-risk patients. Conclusion: Our results suggest that IMDC poor-risk patients benefit most from ICI–TKI combinations, while a proportion of metastatic renal cell carcinoma patients could respond to targeted agent monotherapy.

Immune-based combinations for the treatment of metastatic renal cell carcinoma: a meta-analysis of randomised clinical trials

2021 ◽  
Vol 154 ◽  
pp. 120-127
Author(s):  
Francesco Massari ◽  
Alessandro Rizzo ◽  
Veronica Mollica ◽  
Matteo Rosellini ◽  
Andrea Marchetti ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Meta Analysis ◽  
Randomised Clinical Trials

Risk of toxicity with immunotherapy–tyrosine kinase inhibitors for metastatic renal cell carcinoma: a meta-analysis of randomized controlled trials

2021 ◽  
Author(s):  
Alessandro Rizzo ◽  
Veronica Mollica ◽  
Matteo Santoni ◽  
Matteo Rosellini ◽  
Andrea Marchetti ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Meta Analysis ◽  
Relative Risks

Aim: Few data are available regarding the safety profile of immunotherapy–tyrosine kinase inhibitor (IO-TKI) combinations in metastatic renal cell carcinoma. The authors investigated all-grade and grade 3–4 (G3–4) adverse events in trials comparing IO-TKI combinations with sunitinib monotherapy. Methods: The relative risks of several all-grade and G3–4 adverse events were analyzed. Results: Relative risks were similar between patients receiving IO-TKI combinations versus sunitinib monotherapy. However, the use of IO-TKI combinations was associated with a higher risk of all-grade and G3–4 diarrhea, all-grade hypothyroidism, G3–4 decreased appetite, all-grade and G3–4 aspartate transaminase increase and all-grade and G3–4 alanine transaminase increase. Conclusion: The results of the authors' meta-analysis suggest that risks of treatment-related adverse events should be carefully considered when choosing IO-TKI combinations in metastatic renal cell carcinoma patients.

Genomic alterations to refine prognostication of patients with metastatic renal cell carcinoma.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 626-626 ◽  
Author(s):  
Dominick Bosse ◽  
Wanling Xie ◽  
Aly-Khan A. Lalani ◽  
Guillermo de Velasco ◽  
Martin Henner Voss ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Value ◽  
Kinase Inhibitors ◽  
Cox Regression ◽  
Risk Groups ◽  
Genomic Alterations ◽  
Endothelial Growth Factor

626 Background: The IMDC risk score is a valid and simple tool to prognosticate patients (pts) with metastatic renal cell carcinoma (mRCC). Some non-VHL common genomic alterations may be associated with outcomes. We therefore assessed the prognostic value of most commonly mutated genes in mRCC beside VHL overall, and within IMDC risk groups. Methods: We identified patients treated at Dana-Farber Cancer Institute (n = 65) or part of TCGA (n = 33) who had genomic data available and were treated with first line vascular endothelial growth factor tyrosine kinase inhibitors. Information on genomic alterations (GA) focused on PBRM1, BAP1, SETD2, KDM5C and TP53 was extracted. Cox regression was performed to assess the association of each GA with overall survival (OS), adjusting for IMDC risk groups and age. Results: Overall, 98 pts were identified. 96/98 pts had clear-cell histology. Pts distribution by IMDC risk groups was: 7% good, 58% intermediate, 27% poor and 8% unknown. Mutation rates were 27% PBRM1, 17% BAP1, 29% SETD2, 9% KDM5C and 8% TP53. In multivariable models, there was an association between GA and worse OS for BAP1 and BAP1 or TP53 combined (Table). When stratified by IMDC risk groups, GA in BAP1 or TP53 was associated with shorter median OS in poor risk pts [12.1 mo (95%CI 8.3- 24.0) v. 27.6 mo (95%CI 18.9- 53.4), aHR 4.64 (95%CI 1.32-16.4), p = 0.017] and a trend toward worse median OS in intermediate risk pts [20.5 mo (95%CI 7.4-54.6) v. 36.3 mo (95%CI 21.1, NR), aHR 2.11 (95%CI 0.94-4.74)] compared to pts without GA in BAP1 or TP53. Too few death events were observed in good risk pts to assess the prognostic value of GA in BAP1 or TP53. Conclusions: GA in BAP1 or TP53 are prognostic in mRCC and further discriminate pts with distinct outcomes within IMDC risk groups. Validation in larger dataset is ongoing. [Table: see text]

Adjuvant Tyrosine Kinase Inhibitors in Treatment of Renal Cell Carcinoma: A Meta-Analysis of Available Clinical Trials

2019 ◽  
Vol 17 (2) ◽  
pp. e339-e344 ◽  
Author(s):  
Francesco Massari ◽  
Vincenzo Di Nunno ◽  
Veronica Mollica ◽  
Jeffrey Graham ◽  
Lidia Gatto ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Meta Analysis

scholarly journals The role of PD-L1 expression as a predictive biomarker in advanced renal cell carcinoma: A meta-analysis of randomized clinical trials

2019 ◽  
Vol 30 ◽  
pp. v40
Author(s):  
A. Carretero-Gonzalez ◽  
I. Martín Sobrino ◽  
I. Sáez Sanz ◽  
D. Castellano Gauna ◽  
G.A. De Velasco Oria de Rueda
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Predictive Biomarker ◽  
Advanced Renal Cell Carcinoma
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