Use of typical in-patient blood pressure measurements to detect bevacizumab-induced elevation in systolic pressure after the first infusion.

Abstract

e13622 Background: Hypertension is a mechanism-based toxicity of the antivascular endothelial growth factor (VEGF) agent bevacizumab (Bev). Blood pressure (BP) elevations are a putative biomarker for VEGF inhibition and can be detected 1-8 days after initial treatment with VEGF receptor kinase inhibitors. The earliest time to detect BP changes in patients (pts) receiving Bev is unknown. Methods: BP was measured in hospitalized head and neck cancer pts in 2 clinical trials of Bev added to curative intent therapy. A phase I trial administered Bev on day 2 of each cycle of twice daily radiotherapy with fluorouracil and hydroxyurea (FHX). Complete BP data were available for 21 pts (who received 5 or 10 mg/kg Bev). Another trial randomized 16 pts at 1 institution to receive FHX + 10mg/kg Bev and 7 pts to FHX alone. Over the 6 days inpt treatment in each cycle, BP was measured once every 8 hour shift with a properly sized cuff with a DinaMap PRO400 or similar digital monitor (GE Medical Systems, Milwaukee, WI) by a patient care technician. Retrospectively, mean BP was calculated for each pt for each hospital calendar day. Results: In the phase I trial, the earliest evidence of bev-induced elevation was for the difference between the systolic BP (SBP) on cycle 1 day 3 (mean= 133mmHg; SD 14mmHg) and the baseline BP on cycle 1 day 1 (mean= 126mmHg; SD 11mmHg); mean change = 7mmHg (SD=15mmHg, 95% CI [0, 14], p = 0.04 by paired T-test). A similar effect was seen in cycle 2 but was blunted on subsequent cycles and was not statistically significant for diastolic BP at any cycle. The change in SBP was again detected in pts receiving Bev in the randomized study, mean change = 8mmHg (SD=12mmHg, 95% CI[1, 14], p = 0.03), but was absent in pts receiving FHX alone, mean change = −3.3mmHg (SD=14mmHg, 95% CI [− 16, 9], p = 0.54). There was a statistically significant treatment arm by day interaction for SBP (p = 0.04). Conclusions: With a relatively insensitive BP measurement method these studies detected evidence of a BP-elevating effect of Bev the day after the initial infusion. Studies with larger numbers of pts or more sensitive measurement methods will be needed to confirm the capacity to detect early BP elevations in pts receiving Bev. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories, Amgen, Astellas Pharma, Biomarin, Inc., Daiichi Sankyo, Genentech, Gilead, Millennium, Pfizer Actelion, Bayer, Bristol-Myers Squibb, EMD Serono, Genentech, Gilead, Lilly, Pfizer, Roche Patent pending for use of sorafenib to treat pulmonary hypertension