TY - JOUR
T1 - Diastolic blood pressure as a biomarker of axitinib efficacy in solid tumors
AU - Rini, Brian I.
AU - Schiller, Joan H.
AU - Fruehauf, John P.
AU - Cohen, Ezra E W
AU - Tarazi, Jamal C.
AU - Rosbrook, Brad
AU - Bair, Angel H.
AU - Ricart, Alejandro D.
AU - Olszanski, Anthony J.
AU - Letrent, Kristen J.
AU - Kim, Sinil
AU - Rixe, Olivier
PY - 2011/6/1
Y1 - 2011/6/1
N2 - Purpose: To evaluate if diastolic blood pressure (dBP) ≥90mmHg 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.
AB - Purpose: To evaluate if diastolic blood pressure (dBP) ≥90mmHg 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.
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U2 - 10.1158/1078-0432.CCR-10-2806
DO - 10.1158/1078-0432.CCR-10-2806
M3 - Article
C2 - 21531811
AN - SCOPUS:79957909038
SN - 1078-0432
VL - 17
SP - 3841
EP - 3849
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -