Adjuvant therapy with tyrosine kinase inhibitors for localized and locally advanced renal cell carcinoma: an updated systematic review and meta-analysis

Abstract Background: Hypothyroidism as a predictive factor represent highly controversial in patients with metastatic renal cell carcinoma (mRCC) with tyrosine kinase inhibitors-induced (TKI-induced) hypothyroidism. we aimed to evaluate the predictive value of TKI-induced hypothyroidism for progression-free survival (PFS) in patients with mRCC.Methods: PubMed, Web of Science and Cochrane Library databases were searched with the keywords of "renal cell carcinoma", "hypothyroidism", "tyrosine kinase inhibitor", "sunitinib", "axitinib", "sorafenib" and "pazopanib" until September 2019. The hazard ratio (HR) and 95% confidence interval (CI) of extracted from progression-free survival (PFS) were statistically analyzed by STATA15.1 software. Heterogeneity was assessed by I²value. Publication bias was appraised by the funnel chart, Egger's and Begg's tests.Results: Eighteen studies with more than 1300 patients were included in this meta-analysis. The result demonstrated that TKI-induced hypothyroidism was an effective predictor of longer PFS (HR=0.57,95%CI:0.49-0.66, P＜0.001, I²=34.4%) in patients with mRCC. No significant publication bias was detected.Conclusions: Our analysis harvested from currently available clinical evidence shows that TKI-induced hypothyroidism expressed longer PFS, compared with euthyroidism, among patients with mRCC treated with "sunitinib", "axitinib", "sorafenib" and "pazopanib".

Download Full-text

Association of STAT3 polymorphism with tyrosine kinase inhibitors-induced safety and efficacy in patients with metastatic renal cell carcinoma: a systematic review

AME Medical Journal ◽

10.21037/amj.2017.05.09 ◽

2017 ◽

pp. 69-69

Author(s):

Chenkui Miao ◽

Aiming Xu ◽

Yuxiao Zheng ◽

Chao Liang ◽

Jundong Zhu ◽

...

Keyword(s):

Systematic Review ◽

Renal Cell Carcinoma ◽

Tyrosine Kinase ◽

Cell Carcinoma ◽

Tyrosine Kinase Inhibitors ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitors ◽

Safety And Efficacy

Download Full-text

Efficacy of adjuvant vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (VEGFRi) in renal cell carcinoma (RCC): A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.680 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 680-680

Author(s):

Tobias Engel Ayer Botrel ◽

Otávio Clark ◽

Francisco Flávio Horta Bretas ◽

Marcus V. Sadi ◽

Ubirajara Ferreira ◽

...

Keyword(s):

Systematic Review ◽

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Kinase Inhibitors ◽

Meta Analysis ◽

Locally Advanced ◽

Disease Free Survival ◽

Fixed Effect

680 Background: To perform a systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing the efficacy of adjuvant VEGFRi in locally advanced, non-metastatic clear renal-cell carcinoma (RCC). Methods:Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. We included studies that compared the addition of VEGFRi versus placebo, after nephrectomy. Analyzed endpoints were overall survival (OS) and disease-free survival (DFS). The data extracted from the studies were combined by using Hazard Ratio (HR) or Risk Ratio (RR) with their corresponding Confidence Intervals of 95% (CI95%). Results: Overall, 121 references were identified and screened. The final analysis included 5 trials (S-TRAC, ATLAS, ASSURE, PROTECT and SORCE) comprising 6,128 patients that underwent previous nephrectomy for RCC. The DFS was similar in patients who received VEGFRi (fixed effect: HR=0.94, CI95%=0.87 to 1.03; p=0.19), with no heterogeneity (Chi2 = 4.33, df = 5 (P=0.50); I2 = 0%). Overall survival also was not statistically better in patients who received VEGFR inhibitors (HR=1.01, CI95%=0.90 to 1.15; p=0.84), with no heterogeneity (Chi2= 3.57, df = 5 (P=0.61); I2 = 0%). In the final combined analysis of the higher-risk disease group (pT3, pT4, or N+ disease), patients who received VEGFRi had a longer DFS (fixed effect: HR=0.85, CI95%=0.74 to 0.97; p=0.02), with no heterogeneity (Chi2 = 2.46, df = 3 (P=0.48); I2 = 0%). Overall survival was not statistically different for these higher-risk disease patients (fixed effect: HR=0.93, CI95%=0.74 to 1.16; p=0.5). Conclusions: This is the first meta-analysis including the five available RCTs in the literature (the previous meta-analysis reviewed only four), comparing adjuvant VEGFRi versus placebo in patients submitted to nephrectomy with a locally advanced, non-metastatic RCC. Adjuvant VEGFRi did not increase the OS in this group of patients. Amodest benefit of DFS with the use of adjuvant VEGFR inhibitors was restricted to patients with the highest risk of relapse.

Download Full-text

Testicular metastasis from renal cell carcinoma after nephrectomy and on tyrosine kinase inhibitors therapy: Case report and review

Urologia Journal ◽

10.1177/0391560318818951 ◽

2019 ◽

Vol 86 (2) ◽

pp. 96-98

Author(s):

Alberto De Gobbi ◽

Mario Salvatore Mangano ◽

Giandavide Cova ◽

Claudio Lamon ◽

Luigino Maccatrozzo

Keyword(s):

Renal Cell Carcinoma ◽

Tyrosine Kinase ◽

Cell Carcinoma ◽

Tyrosine Kinase Inhibitors ◽

Renal Cell ◽

Kinase Inhibitors ◽

Web Of Science ◽

Locally Advanced ◽

Renal Clear Cell Carcinoma ◽

Primary Therapy

Renal cell carcinoma has extremely heterogeneous presentation at the diagnosis: it may present as a confined organ disease, locally advanced, metastatic to locoregional lymph nodes or with single or multiple systemic metastases. Since chemotherapy and radiation therapy have not demonstrated efficacy either in primary therapy or in neo-adjuvant or adjuvant therapy for renal clear cell carcinoma, targeted agents like tirosine kinase inhibitors were developed and are largely used in locally advanced and metastatic renal cell carcinoma. Here, we present a rare case of ipsilateral renal cell carcinoma testicle metastasis, after radical nephrectomy and during tyrosine kinase inhibitors therapy. In addition, a retrospective search in PubMed, ScienceDirect, and Web of Science database on testicular metasteses from renal cell carcinoma under tyrosine kinase inhibitors therapy was performed.

Download Full-text