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

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.

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 elevationsversusbaseline, in apost hocanalysis of a phase III trial of 1102 patients with renal cell carcinoma (RCC) randomized to pazopanib or sunitinib (COMPARZ study).

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 mmHgversusbaseline). 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.

There was a significant variability in the incidence, number and type of predictors of AVEGF-HT, using six different criteria, in apost hocanalysis 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.

Therapeutic advances in medical oncology. 2018 Feb 05*** epublish ***

Arduino A Mangoni, Ganessan Kichenadasse, Andrew Rowland, Michael J Sorich

Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide, Australia., Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University, Adelaide, Australia., Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Adelaide, Australia; Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University, Adelaide, Australia.