April 30, 2011Open Access
Diastolic Blood Pressure as a Biomarker of Axitinib Efficacy in Solid Tumors
Key Result
Experiencing a diastolic blood pressure ≥90 mm Hg during axitinib treatment for solid tumors was associated with a significantly lower risk of death (adjusted HR 0.55; 95% CI 0.39-0.77; P<0.001).
Study Design
Type
Cohort (n=230)
Multicenter
Yes
Structured PICO
Does developing dBP ≥90 mm Hg during axitinib treatment predict improved survival and response rates in patients with solid tumors?
P
Population
230 patients with solid tumors and baseline BP ≤140/90 mm Hg receiving single-agent axitinib, evaluated retrospectively across 5 phase II studies.
E
Exposure
Axitinib treatment resulting in at least 1 in-clinic diastolic blood pressure (dBP) ≥90 mm Hg.
C
Comparator
Axitinib treatment with dBP <90 mm Hg throughout therapy.
O
Outcome
Median overall survival (mOS), median progression-free survival (mPFS), objective response rate (ORR), and adverse events.hard clinical
The development of diastolic blood pressure ≥90 mm Hg during axitinib treatment is associated with significantly improved overall survival and objective response rates in patients with solid tumors.
Main Result
Hazard Ratio: 0.55 (95% CI 0.39–0.77)
p-value: p=< 0.001
Abstract
PURPOSE: To evaluate if diastolic blood pressure (dBP) ≥90 mm Hg during axitinib treatment is a marker of efficacy. EXPERIMENTAL DESIGN: The relationship between dBP ≥90 mm Hg and efficacy was retrospectively explored across 5 phase II studies of single-agent axitinib for the treatment of 4 different tumor types. All patients had baseline BP ≤140/90 mm Hg and were stratified into 2 groups based on in-clinic BP measurements after initiating therapy: those with dBP <90 mm Hg throughout therapy and those with at least 1 dBP ≥90 mm Hg. Median overall survival (mOS), median progression-free survival (mPFS), objective response rate (ORR), and adverse events were evaluated by dBP group in individual and pooled analyses. RESULTS: Two-hundred thirty patients were evaluated. Patients with dBP ≥90 mm Hg had a significantly lower relative risk of death than those with dBP <90 mm Hg adjusted HR (95% CI) = 0.55 (0.39, 0.77); P < 0.001. The relative risk of progression was also lower in patients with dBP ≥90 mm Hg HR (95% CI) = 0.76 (0.54, 1.06), P = 0.107, and ORR was significantly higher (43.9% vs. 12.0%; P < 0.001). In an 8-week landmark analysis, mOS (25.8 vs. 14.9 months) and mPFS (10.2 vs. 7.1 months) were greater for patients in the ≥90 mm Hg group. Adverse events were similar between groups. CONCLUSIONS: Axitinib efficacy correlated with dBP ≥90 mm Hg. Further investigation of dBP as a predictive biomarker of efficacy in patients receiving axitinib is warranted.