Predictors of anti-VEGF drug-induced hypertension using different hypertension criteria: a secondary analysis of the COMPARZ study

Abstract

Background:There is inconsistency in the criteria used to define anti-vascular endothelial growth factor (VEGF) drug-induced hypertension (AVEGF-HT) in published studies. It is unknown whether specific patient characteristics similarly predict AVEGF-HT using different criteria.Methods:We assessed the associations between clinical and demographic factors (n = 22) and AVEGF-HT, using six criteria based on predefined on-treatment blood pressure (BP) thresholds or absolute BP elevations versus baseline, in a post hoc analysis of a phase III trial of 1102 patients with renal cell carcinoma (RCC) randomized to pazopanib or sunitinib (COMPARZ study).Results:The cumulative incidence of AVEGF-HT at any time while on treatment ranged between 14.8% [criterion: grade ⩾3 toxicity, National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0] and 58.8% (criterion: absolute systolic BP increase ⩾20 mmHg versus baseline). After adjusting for anti-VEGF treatment and baseline BP, the number of significant (p < 0.05) predictors ranged between one (criterion: absolute systolic BP increase ⩾20 mmHg, on-treatment systolic BP ⩾140 mmHg and diastolic BP ⩾90 mmHg) and nine (criterion: grade ⩾3 toxicity, NCI CTCAE v3.0). Age, use of antidiabetic drugs and use of antihypertensive drugs each significantly predicted four AVEGF-HT criteria. By contrast, sex, smoking, heart rate, proteinuria, Karnofsky performance status, and use of thiazide diuretics did not predict any criterion.Conclusions:There was a significant variability in the incidence, number and type of predictors of AVEGF-HT, using six different criteria, in a post hoc analysis of the COMPARZ study. The use of specific criteria might affect the assessment of the interaction between anti-VEGF drugs, AVEGF-HT and cancer outcomes.

Therapy Management Using Modified 2-Weeks-On/1-Week-Off Dosing Schedule in Patients With Metastatic Renal Cell Carcinoma Receiving Sunitinib: A Hypothetical, Illustrative Case Scenario

“…The trial did not reach the primary endpoint of achieving lower than grade 3 AEs for fatigue, diarrhea, and HFS in patients on schedule 2/1; however, the investigators reported similar rates (∼25%) of these grade 3 AEs as has been historically reported for patients on schedule 4/2. In addition, they noted that no grade 4 AEs were reported for patients on schedule 2/1 and the discontinuation rate for patients was 10%, which compares favorably with the original pivotal trial data reported by Motzer and colleagues (2007) and the more recent COMPARZ trial data, wherein the discontinuation rates were 20% for patients on schedule 4/2 ( Jonasch et al, 2018 ; Mangoni, Kichenadasse, Rowland, & Sorich, 2018 ). Jonasch and colleagues also reported efficacy results (median progression-free survival of 13.7 months; 95% confidence interval = 10.9–16.3 months) that were better than expected based on the prognostic classifications of the patient population (78% of patients were intermediate- or poor-risk according to Memorial Sloan Kettering Cancer Center criteria; Jonasch et al, 2018 ), suggesting that, at the least, schedule 2/1 is not associated with a reduction in efficacy ( Mangoni et al, 2018 ).…”

Trends in Renal-Cell Carcinoma Incidence and Mortality in the United States in the Last 2 Decades: A SEER-Based Study

“…The introduction of vascular endothelial growth factor (VEGF) inhibitors (also known as antiangiogenics) and checkpoint inhibitors for advanced cases of RCC has significantly impacted the survival of these patients (39)(40)(41)(42). The Food and Drug Administration (FDA) approval of sorafenib and sunitinib in 2005 and 2006, respectively, followed by the approval of more antiangiogenic therapies have been a pivotal point in advanced RCC treatment.…”

Both New-Onset and Pre-Existing Hypertension Indicate Favorable Clinical Outcomes in Patients Treated With Anti-Vascular Endothelial Growth Factor Therapy

“…Preexisting HTN, older age, and obesity were risk factors for increased blood pressure after VSP inhibitor administration. 42,43 Half the patients with 2 of the above risk factors and 60% of those with all 3 risk factors developed HTN after anti-VEGF therapy. 42 In the present study, 62% of the total study population and >70% of those with preexisting HTN were aged ≥70 years, and the age distribution in the present study was higher than in other clinical trials.…”