Hypertension as a prognostic factor in metastatic renal cell carcinoma treated with tyrosine kinase inhibitors: a systematic review and meta-analysis

Abstract

Background Conflicting evidence exists regarding the effect of hypertension on the prognosis of metastatic renal cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors (TKIs). This study aimed to assess the predictive value of TKIs-induced hypertension in patients with mRCC. Methods This study was registered in PROSPERO (CRD42019129593). PubMed, Embase, Web of Science and the Cochrane Library database were searched with terms: “renal cell carcinoma”, “hypertension”, “blood pressure”, “tyrosine kinase inhibitor”, “sunitinib”, “axitinib”, “sorafenib” and “pazopanib” until March 21, 2019. Hazard Ratios (HR) and 95% confidence intervals (CI) for progression-free survival (PFS) or overall survival (OS) were extracted and analyzed with Stata 15.0 software. Heterogeneity was assessed using the I 2 value. Meta-regression, subgroup analysis and sensitivity analysis were also performed to explore heterogeneity. Publication bias was assessed with funnel plots and precisely assessed by Egger’s and Begg’s tests. The quality of evidence of outcomes was generated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results A total of 4661 patients from 22 studies were included in the study. The results showed that the increase of blood pressure was an effective predictor for longer PFS (HR = 0.59, 95% CI: 0.48–0.71, p < 0.001; I 2 = 77.3%) and OS (HR = 0.57, 95% CI: 0.45–0.70, p < 0.001; I 2 = 77.4%) of patients with mRCC. Subgroup analysis revealed that patients receiving sunitinib and pazopanib could have longer PFS and OS. Conclusions This study indicated that TKIs-induced hypertension may be a good predictor for better prognosis of patients with mRCC receiving TKIs treatment, especially using sunitinib or pazopanib. Electronic supplementary material The online version of this article (10.1186/s12894-019-0481-5) contains supplementary material, which is available to authorized users.

Individualization of Dose and Schedule Based On Toxicity for Oral VEGF Drugs in Kidney Cancer

“…Several retrospective series have shown that patients that do not need dose/schedule changes from the standard 50 mg 4/2 sunitinib schedule to manage toxicity have a worse outcome. This is consistent with early report showing a better outcome in mRCC patients that developed hypertension, hypothyroidism or hand foot syndrome while on VEGFR-TKI therapy [26,27].…”

Association between tyrosine‐kinase inhibitor induced hypertension and treatment outcomes in metastatic renal cancer

“…In this study, we have demonstrated potential association between TKI-induced hypertension and patient outcomes for PFS and 6 month and 12 month survival. Consistent with previous studies, approximately half of the patients developed TKI-induced hypertension 9,14. Due to a large proportion of patients still alive at the time of data collection (63%), overall survival (OS) was not able to be evaluated.…”

“…In all the published studies, hypertension was easily managed with the introduction of an antihypertensive agent and rarely required discontinuation of TKI. 9,14 The best pharmacological therapy for TKI-induced hypertension is unclear and it is also unknown if it should be managed any differently from essential hypertension. There are no standard guidelines to assist with evaluation, diagnosis, monitoring, and management of TKI-induced hypertension.…”

“…8 Clinical trials have shown an objective response rate (ORR) of 30% to 40% to TKIs. 9 Unfortunately TKIs are associated with several adverse-events, having a detrimental effect on quality of life, but do not benefit every patient. 10 TKIs related adverse-events are due to the inhibition of VEGF receptors as well as off target interactions with other TKI receptors.…”

“…Previous studies have indicated that the occurrence of druginduced adverse-events may have a role as clinical biomarkers in patients with metastatic RCC that are treated with TKI therapy. 9,11,12 The purpose of the current study is to review medical records of patients with newly diagnosed metastatic RCC who were treated at a single institution with first-line TKIs and examine for the presence (if any) of an association between TKI-induced hypertension and treatment outcomes.…”