Hypertension a Good Sign in Patients Receiving Sunitinib

Caroline Helwick

April 2011, Vol 2, No 2 - Genitourinary Cancers Symposium

Suzanne George, MDSan Francisco, CA—For patients with gastrointestinal stromal tumors (GIST) being treated with sunitinib (Sutent), the development of hypertension during treatment was associated with a survival benefit, said Suzanne George, MD, Dana-Farber Cancer Institute, Boston, at the 2011 Gastrointestinal Cancers Symposium.

Hypertension appears to be a class effect of vascular endothelial growth factor (VEGF) signaling pathway inhibitors and has been proposed as a biomarker of clinical outcomes for these agents. Sunitinib is a multitargeted inhibitor of VEGF receptors and the other receptor tyrosine kinase approved for the treatment of GIST after failure with imatinib (Gleevec) treatment.

In patients receiving sunitinib for renal-cell carcinoma, the occurrence of hypertension was a significant predictor of efficacy. “Sunitinib-associated hypertension appeared to be correlated with improved clinical outcomes, which support the hypothesis that hypertension may be a biomarker for antitumor efficacy,” Dr George said.

Safety, Efficacy of Hypertension in GIST
The current study retrospectively explored the association between hypertension and outcomes in 2 prospective clinical trials of sunitinib in GIST. The efficacy analysis included 319 patients; the safety analysis included 1565 patients. Hypertension was defined as a maximum systolic blood pressure (BP) ≥140 mm Hg and diastolic BP ≥90 mm Hg.

The development of hypertension at any time during treatment was associated with improved clinical outcomes, Dr George reported.

In the final multivariate analysis, investigators analyzed outcomes separately, according to maximum diastolic and systolic BP. Median progression free survival and median overall survival were significantly improved with elevated systolic or diastolic BP (Table).

In all comparisons, the development of hypertension was associated with a highly significant 50% reduction in recurrence and death. The superiority of these clinical outcomes was not compromised by treatment with antihypertensive medications, Dr George said.

Hypertension-associated adverse events were rare, although patients with hypertension had a slightly greater frequency and severity of cardiovascular adverse events than those without hypertension. Treating hypertension in this patient population is necessary as in other populations.

In addition to finding hypertension as a marker for good outcomes in this patient population in terms of cancerrelated survival, Dr George said, “the message is that physicians should monitor for hypertension early in treatment, because its mean onset is 4 to 6 weeks, and if they see it, they need to treat it.”