Adjuvant therapy with tyrosine kinase inhibitors for localized and locally advanced renal cell carcinoma: an updated systematic review and meta-analysis
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, metaanalýza, práce podpořená grantem, systematický přehled
PubMed
34400065
DOI
10.1016/j.urolonc.2021.07.022
PII: S1078-1439(21)00340-9
Knihovny.cz E-zdroje
- Klíčová slova
- Adjuvant Therapy, Meta-Analysis, RCC, Renal Cell Carcinoma, TKI,
- MeSH
- adjuvantní chemoterapie metody MeSH
- inhibitory proteinkinas farmakologie terapeutické užití MeSH
- karcinom z renálních buněk farmakoterapie mortalita patologie MeSH
- lidé MeSH
- nádory ledvin farmakoterapie mortalita patologie MeSH
- přežití bez známek nemoci MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- systematický přehled MeSH
- Názvy látek
- inhibitory proteinkinas MeSH
PURPOSE: Tyrosine kinase inhibitors (TKIs) have been widely used in the management of patients with metastatic renal cell carcinoma (RCC). However, the use of systemic therapies in the adjuvant setting of localized and locally advanced RCC has shown conflicting results across the literature. Therefore, we aimed to conduct an updated systematic review and meta-analysis comparing the efficacy and safety of TKIs in the adjuvant setting for patients with localized and locally advanced RCC. MATERIALS AND METHODS: The MEDLINE and EMBASE databases were searched in December 2020 to identify phase III randomized controlled trials of patients receiving adjuvant therapies with TKI for RCC. Disease-free survival (DFS) and overall survival (OS) were the primary endpoints. The secondary endpoints included treatment-related adverse events (TRAEs) of high and any grade. RESULTS: Five trials (S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our meta-analysis comprising 6,531 patients. The forest plot revealed that TKI therapy was associated with a significantly longer DFS compared to placebo (pooled HR: 0.88, 95% CI: 0.81-0.96, P= 0.004). The Cochrane's Q test (P = 0.51) and I2 test (I2 = 0%) revealed no significant heterogeneity. Adjuvant TKI was not associated with improved OS compared to placebo (pooled HR: 0.93, 95% CI: 0.83-1.04, P= 0.23). The Cochrane's Q test (P = 0.74) and I2 test (I2 = 0%) revealed no significant heterogeneity. The forest plot revealed that TKI therapy, compared to placebo, was associated with higher rates of high grade TRAEs (OR: 5.20, 95% CI: 4.10-6.59, P< 0.00001) as well as any grade TRAEs (OR: 3.85, 95% CI: 1.22-12.17, P= 0.02). The Cochrane's Q tests (P < 0.0001 and P < 0.00001, respectively) and I2 tests (I2 = 79% and I2 = 90%, respectively) revealed significant heterogeneity. CONCLUSIONS: The findings of our analyses suggest an improved DFS in patients with localized and locally advanced RCC receiving adjuvant TKI as compared to placebo; however, this did not translate into any significant OS benefit. Additionally, TKI therapy led to significant toxicity. Adjuvant TKI does not seem to offer a satisfactory risk and/orbenefit balance for all patients. Select patients with very poor prognosis may be considered in a shared decision-making process with the patient. With the successful arrival of immune-based therapies in RCC, these may allow a more favorable risk/benefit profile.
Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria
Institute for Urology and Reproductive Health Sechenov University Moscow Russia
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