Physicians and nursing staff effectively managed hypertension—an established target-related side effect of vascular endothelial growth factor receptor (VEGFR) inhibitors—using home blood pressure monitors and a treatment algorithm in patients enrolled in a phase 2 randomized discontinuation trial of tivozanib, a potent and selective inhibitor of all three VEGFR kinases.
The objective of the study was to determine activity of tivozanib in renal cell carcinoma (RCC) and evaluate its safety and tolerability, including management of observed toxicities, said Brooke Esteves, BSN, RN, AVEO Pharmaceuticals, Inc, Cambridge, Massachusetts, and colleagues. The study included 272 patients with locally advanced or metastatic RCC of any histology who had not previously received VEGF-targeted therapy. Tivozanib 1.5 mg/day was administered on a 3 weeks on/1 week off cycle, and independent radiology reviewers evaluated response using standard RECIST criteria, Esteves told those attending the Oncology Nursing Society 36th Annual Congress.
Blood pressure was measured in the clinic weekly during the first two cycles, and on day 1 of subsequent cycles. Study oncologists managed hypertension (defined as systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg) using a treatment algorithm involving standard antihypertensives and/or reduction or interruption of the study medication.
Tivozanib was found to be effective and well tolerated. In all patients, treatment with tivozanib resulted in a median progression-free survival (PFS) of 11.8 months; in patients with clear cell histology and prior nephrectomy, median PFS was 14.8 months. The most common treatment-related adverse event was hypertension (50%), and the most common grade 3 or higher treatment-related adverse events were hypertension (9%), asthenia (2%), diarrhea (1%), and fatigue (1%).
Hypertension, which was readily managed utilizing the study algorithm, was associated with significantly longer PFS compared with patients without hypertension (diastolic BP, 17.6 vs 8.3 months, respectively; systolic BP, 14.8 vs 8.9 months, respectively; P = .01 for both). Since hypertension is a common and manageable side effect of VEGFR inhibitors, patients should be educated before beginning treatment with tivozanib, Esteves noted.
Therapies that inhibit the VEGF pathway, such as tivozanib, disrupt tumor angiogenesis, which is critical for tumor growth. The efficacy and acceptable tolerability observed with tivozanib monotherapy has led to its evaluation in combination with temsirolimus (RCC), FOLFOX6 (colorectal cancer), paclitaxel (breast cancer), everolimus (colorectal cancer), and capecitabine (solid tumors), the researchers concluded.