Hypertension and targeted therapies for cancer

Objective: Hypertension represents an on-target class effect of vascular endothelial factor signalling-pathway inhibitors and sunitinib is a multitargeted receptor tyrosine kinase inhibitor approved for the treatment of metastatic Renal Cell Carcinoma (RCC) We evaluated the association of sunitinib induced hypertension with clinical outcomes in patients with RCC. Methods: We consecutively included 67 RCC patients treated with sunitinib (50mg/day p.o for 4 weeks,followed by a 2-week rest) with well-controlled Blood Pressure (BP) at baseline. BP was measured in the clinic on days 1 and 28 of each 6-week cycle. Hypertension (HTN) was graded according to the European Society Hypertension Criteria. Progression –free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods. Results: The overall incidence of all-grade and high-grade HTN were 46% and 9% respectively.Median time to onset of ≥ Gr 2 HTN was 7.1 weeks. response rates were 37% for patients with Gr 1 HTN compared to 77% for patients with Gr ≥2 HTN (p<0.002).Median PFS was14.3 months (95% CI: 12.3-17.4) vs 4.1 months (95% CI:2.2-6.1) and median OS was 29.3 months (95% CI: 24,1-33.8) vs 8.3 months (95% CI: 5.1-11,2).In a multivariate analysis HTN was an independent predictor of overall survival (HR: 0.48 95% CI; 0.32-0.68, p<0.03). Conclusion: Development of hypertension appears to be associated with improved clinical outcomes in cancer patients treated with antiangiogenic therapy and HTN may be a strong predictor for cancer treatment efficacy.