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| |  Hypertension May Be Biomarker for Sunitinib Efficacy: Presented at ASCO-GU By Fred Gebhart SAN FRANCISCO -- March 8, 2010 -- Clinicians’ view of hypertension associated with sunitinib treatment may be changing. While elevated blood pressure associated with the use of sunitinib and other vascular endothelial growth factor (VEGF) agents has been reported as an adverse event, new data suggest that systolic blood pressure >140 mm Hg and diastolic blood pressure >90 mm Hg may indicate efficacy. “The data suggest hypertension associated with sunitinib treatment can be a biomarker for antitumour efficacy in these patients,” said Brian Rini, MD, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio. “Hypertension, which can be managed, is commonly associated with VEGF inhibitors.” Dr. Rini was the lead author on a retrospective analysis of multiple clinical trials investigating the use of sunitinib in advanced renal cell carcinoma (RCC). The data were reported during a poster presentation here on March 7 at the 2010 Genitourinary Cancers Symposium (ASCO-GU). The researchers analysed pooled data from 3 clinical trials of sunitinib for first-line and second-line treatment in a total of 544 patients. The safety portion of the analysis was expanded to include 4,917 patients in an extended-access trial in metastatic RCC. Hypertension was defined as maximum and mean systolic blood pressure of 140 mm Hg or greater and maximum and mean diastolic blood pressure of 90 mm Hg or greater. Cancer outcomes were measured by progression-free survival, overall survival, and objective response rate. Antihypertensive medications and/or sunitinib dose reduction were used to manage hypertension as allowed in the original study protocols. The analysis found that 81% of the 544 patients in the efficacy analysis had systolic hypertension and 67% had diastolic hypertension. Patients who became hypertensive during treatment reached systolic hypertension during the first treatment cycle and diastolic hypertension during the second cycle. The relative dose intensity of sunitinib treatment did not correlate with maximum systolic blood pressure. There was a strong association between maximum blood pressure and survival. Patients with maximum systolic blood pressure of >=140 mm Hg had a median overall survival of 30.9 versus 7.2 months without hypertension (P < .0001). Patients with a maximum diastolic blood pressure of >=90 mm Hg had a median overall survival of 32.2 versus 14.9 months without hypertension (P < .0001). The median progression-free survival for patients with systolic blood pressure of >=140 mm Hg was 12.5 versus 2.5 months without systolic hypertension (P < .0001). The median progression-free survival for patients with diastolic blood pressure of >=90 mm Hg was 13.4 versus 5.3 months without diastolic hypertension (P < .0001). The overall survival advantage for hypertension translates to a hazard ratio of 0.332 for systolic blood pressure of >=140 mm Hg and 0.585 for diastolic blood pressure of >=90 mm Hg (P < .0001). The hazard ratio for overall survival with systolic blood pressure of >=140 mm Hg is 0.603 and with diastolic blood pressure of >=90 mm Hg is 0.992. Adverse cardiovascular, cerebrovascular, and ocular events of grade 3 or higher were similar in patients with and without systolic hypertension. There was a slight increase in renal events associated with hypertension, but events were generally tolerable and manageable, and the clinical importance of the increase is not clear. Multivariate analysis found that treatment-induced hypertension is a significant and independent predictor of survival benefit (P < .001). Researchers concluded that patients on sunitinib should be monitored for hypertension and treated for elevated blood pressure as needed. They also noted that further study is needed to uncover the mechanism linking hypertension and treatment efficacy and that the effect should be tested in prospective clinical trials. The conference is sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Therapeutic Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO). [Presentation title: Hypertension as a Biomarker of Efficacy in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib. Abstract 312]
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