In a retrospective analysis, pazopanib-induced hypertension (HTN) did not correlate with outcome in pazopanib-treated soft tissue sarcoma (STS) patients, meaning the occurrence of HTN cannot serve as a biomarker in this setting, according to an article published online ahead of print in the European Journal of Cancer.1
The rationale for the study was that HTN is an on-target effect of vascular endothelial growth factor (VEGF)-receptor inhibitors, such as pazopanib. Reliable biomarkers for the efficacy of pazopanib in soft-tissue are lacking.
Researchers sought to evaluate associations between pazopanib-induced hypertension and antitumor efficacy in patients with metastatic non-adipocytic STS.
Associations were retrospectively assessed across 2 prospective studies: European Organisation for Research and Treatment of Cancer (EORTC) study 62043 and 62072, in metastatic patients who received pazopanib 800 mg daily. Enrollment was restricted to patients with a baseline blood pressure (BP) < 150/90 mmHg. BP was measured monthly.
The effect of HTN developing in patients without baseline anti-HTN medications was assessed on progression-free survival (PFS) and overall survival (OS) using a landmark analysis stratified by study; univariately using the Kaplan-Meier method and a log-rank test, and in a multivariate Cox regression model after adjustment for important prognostic factors.
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Findings showed that of 337 patients, 21.7% received anti-HTN medications at baseline and had a similar PFS and OS compared to those who did not. In patients without baseline anti-HTN medications, 38.6% developed HTN, mostly within the first 5 weeks of receiving pazopanib.
There was no effect on PFS or OS from occurrence of HTN within 5 weeks of treatment expressed either in NCI-CTCAE criteria or as maximal differences from baseline in systolic and diastolic BP.
- Duffaud F, Sleijfer S, Litiere S, et al; Hyptertension (HTN) as a potential biomarker of efficacy in pazopanib-treated patients with advanced non-adipocytic soft tissue sarcoma. A retrospective study based on European Organisation for Research and Treatment of Cancer (EORTC) 62043 and 62072 trials. [published online ahead of print August 25, 2015]. EJC. doi: 10.1016/j.ejca.2015.08.002.