Late-Onset Hypertension Is Associated With Improved Clinical Outcomes in Cancer Patients Treated With Sunitinib

Abstract

Background: Sunitinib is a multitargeted tyrosine kinase inhibitor with antiangiogenic and antitumor effects. Angiogenesis inhibitor-induced hypertension results from both short-term changes in vasoactive substances and by long-term microvascular rarefaction. This study investigated the relationship between late-onset hypertension and prognosis of cancer patients treated with sunitinib.

Methods and Results: We retrospectively analyzed time to hypertension and time to disease progression in patients treated with sunitinib. Of 92 patients, 62 were eligible for analysis. Clinical outcomes were compared among patients who remained normotensive, those who developed hypertension within 3 months, and those who developed hypertension after 3 months following the initiation of sunitinib treatment. At baseline, blood pressure was below 140/90 mmHg in all groups. Sunitinib was administered for renal cell carcinoma (74.2%), pancreatic neuroendocrine tumor (14.5%), and gastrointestinal stromal tumor (11.3%). Hypertension developed in 27 (43.5%) patients after sunitinib treatment. The severity of hypertension did not differ between the early onset (within 3 months) and late-onset (after 3 months) groups. Progression-free survival for all cancer types and for renal cell carcinoma was significantly longer in the late-onset hypertension group than in the normotensive or early onset hypertension groups.

Conclusions: Late-onset hypertension was associated with prolonged progression-free survival in sunitinib-treated patients. Long-term structural changes in the vasculature may underlie the association between late-onset hypertension and a better prognosis.