Highlights
- •Hypertension is a commonly observed adverse event with angiogenesis inhibitors.
- •We explore hypertension as a predictive marker with pazopanib and sunitinib in renal cell carcinoma.
- •In data from three trials, hypertension was not associated with efficacy outcomes.
Abstract
Aim
Pazopanib, an oral antiangiogenic agent, is associated with improved outcomes in patients
with metastatic renal cell carcinoma. In this retrospective analysis, we explore hypertension,
an on-target adverse event, as a predictive marker.
Methods
Data from the pazopanib arm of the phase III COMPARZ trial (NCT00720941) comprised
the test set. Pooled data from phase II (NCT00244764) and III (NCT00334282) pazopanib
trials comprised the validation set. Data from the sunitinib arm of COMPARZ were analysed
separately. Measures of efficacy were response rate, progression-free survival (PFS),
and overall survival (OS). Mean arterial blood pressure (MAP) was the primary metric,
and systolic hypertension (S-HTN) and diastolic hypertension (D-HTN) were secondary
metrics; 4- and 12-week landmark analyses were performed.
Results
Analyses revealed no significant associations at the landmarks between response and
MAP. We observed a trend towards improved PFS with S-HTN at week 4 (hazard ratio [HR] = 0.79,
P = 0.060) and week 12 (HR = 0.75, P = 0.073) among pazopanib-treated patients in COMPARZ. This trend was not confirmed
at week 12 in the validation set or in sunitinib-treated patients. In the test set,
there was a trend towards increased OS in patients with S-HTN by week 4 (HR = 0.76,
P = 0.062) and with D-HTN by week 4 (HR = 0.71, P = 0.016) but not by week 12. No significant differences in OS were observed in sunitinib-treated
patients for S-HTN or D-HTN.
Conclusion
Neither hypertension nor any blood pressure elevation above baseline was associated
with efficacy outcomes of pazopanib or sunitinib. Accordingly, management of tyrosine
kinase inhibitor-induced hypertension is unlikely to compromise outcome.
Keywords
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Article info
Publication history
Published online: December 14, 2015
Accepted:
October 7,
2015
Received in revised form:
September 24,
2015
Received:
July 17,
2015
Identification
Copyright
© 2015 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
