title: Hypertension among patients with renal cell carcinoma receiving axitinib or sorafenib: analysis from the randomized phase III AXIS trial.
abstract: Inhibitors of the vascular endothelial growth factor (VEGF) pathway frequently induce hypertension when used to treat patients with advanced renal cell carcinoma (RCC). This analysis characterizes hypertension and hypertension-related events in patients treated with the VEGF pathway inhibitors axitinib or sorafenib in the AXIS trial. AXIS was a randomized phase III study of axitinib versus sorafenib in patients with metastatic RCC following failure of one prior systemic regimen. Patients with uncontrolled hypertension were excluded, but patients with hypertension controlled with antihypertensive medication were allowed to participate. Guidelines for hypertension management included adjustment or addition of antihypertensive medications and/or axitinib or sorafenib dose reductions, interruptions, or discontinuations. Treatment-emergent all-causality hypertension occurred in 145 (40.4 %) axitinib-treated patients (N = 359) and 103 (29.0 %) sorafenib-treated patients (N = 355), with grade 3 hypertension reported in 55 (15.3 %) and 38 (10.7 %) patients, respectively, and grade 4 hypertension reported in one (0.3 %) patient in each arm. Hypertension-related events led to axitinib dose interruptions (n = 46; 12.8 %), dose reductions (n = 16; 4.5 %), or discontinuations (n = 1; 0.3 %). Approximately 50 % of axitinib-treated patients with grade 3 or 4 hypertension continued treatment for ≥ 9 months. Hypertension-related sequelae occurred in <1 % of axitinib-treated patients. Hypertension was more frequently observed during treatment with axitinib than sorafenib in patients with RCC, but axitinib-induced hypertension rarely led to treatment discontinuation or cardiovascular sequelae. Recommendations for monitoring blood pressure and managing hypertension during axitinib therapy are presented.
authors.affiliation: Cleveland Clinic Taussig Cancer Institute, Cleveland Clinic Main Campus, Mail Code R35, 9500 Euclid Avenue, Cleveland, 44195, OH, USA, rinib2@ccf.org.
authors.forename: Brian I
authors.initials: BI
authors.lastname: Rini
authors.forename: David I
authors.initials: DI
authors.lastname: Quinn
authors.forename: Michael
authors.initials: M
authors.lastname: Baum
authors.forename: Laura S
authors.initials: LS
authors.lastname: Wood
authors.forename: Jamal
authors.initials: J
authors.lastname: Tarazi
authors.forename: Brad
authors.initials: B
authors.lastname: Rosbrook
authors.forename: Lillian Shahied
authors.initials: LS
authors.lastname: Arruda
authors.forename: Laura
authors.initials: L
authors.lastname: Cisar
authors.forename: W Gregory
authors.initials: WG
authors.lastname: Roberts
authors.forename: Sinil
authors.initials: S
authors.lastname: Kim
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D000077784:Axitinib; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D007093:Imidazoles / Q000009:adverse effects*; D007191:Indazoles / Q000009:adverse effects*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000009:adverse effects*; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D000077784:Axitinib