Pharmacoepidemiology of clinically relevant hypothyroidism and hypertension from sunitinib and sorafenib.

Abstract

9149 Background: Sunitinib (SUN) and sorafenib (SOR) are oral tyrosine kinase inhibitors approved for renal cell carcinoma and gastrointestinal stromal tumors (SUN) and hepatocellular carcinoma (SOR). Sporadic reports of thyroid dysfunction and hypertension (HTN) have been made with these agents. Determination of the true side effect incidence will allow for more efficient monitoring and treatment recommendations. Methods: An observational cohort study was performed using de-identified pharmacy claims data from 2006 to 2009 to evaluate patients (pts) who were prescribed SUN, SOR or capecitabine (CAP). The primary outcome was time to first prescription for thyroid replacement (TR) or HTN treatment. CAP was used as a comparison group for drug-induced hypothyroidism or HTN. Pts were included if they had at least 2 consecutive prescriptions or 45 days of consecutive therapy. Exclusion criteria included presence of concurrent prescriptions for other oral cancer therapies or active prescriptions for TR or HTN therapy. Hazard ratios (HR) with 95% confidence intervals (CI) were estimated by cox proportional hazards models adjusted for age, sex and chronic disease score. Results: A total of 20,061 pts were eligible for evaluation of TR therapy, 1,965 receiving SUN, 1,790 SOR and 16,306 CAP. TR therapy was initiated in 11.6% of those receiving SUN (HR 16.77, CI 13.54, 20.76), 2.6% SOR (HR 3.47, CI 2.46, 4.98) and 1% CAP The median time for needing TR therapy was 4 months. A total of 14,468 pts were eligible for evaluation of HTN therapy, 1,207 SUN, 1,102 SOR, and 12,159 CAP. HTN therapy was initiated in 21% of those receiving SUN (HR 4.91 CI 4.19, 5.74), 14% SOR (HR 3.25, CI 2.69, 3.91), and 5% capecitabine. The median time for needing HTN therapy was 2 months. Conclusions: Pts receiving SUN and SOR have a similar, but elevated, risk of clinically relevant HTN. Clinically relevant hypothyroidism is more than 4 times more common with SUN than SOR. Clinically relevant hypothyroidism usually occurs between 1 and 7 months after the initiation of SUN or SOR therapy. This data provides robust measures of the incidence of these clinically actionable adverse events and implies mechanistic distinctions between the two agents. No significant financial relationships to disclose.