Pharmacoepidemiology of Clinically Relevant Hypothyroidism and Hypertension from Sunitinib and Sorafenib.

BACKGROUND: Thyroid dysfunction and hypertension (HTN) have been sporadically reported with sunitinib (SUN) and sorafenib (SOR). Determination of the side effect incidence will enhance monitoring and management recommendations.

METHODS: An observational cohort study was performed using deidentified pharmacy claims data from a 3-year period to evaluate patients prescribed SUN, SOR, or capecitabine (CAP; comparison group). The primary outcome was time to first prescription for thyroid replacement or HTN treatment. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox proportional hazards models.

RESULTS: A total of 20,061 patients were eligible for evaluation of thyroid replacement therapy, which was initiated in 11.6% of those receiving SUN (HR, 16.77; 95% CI, 13.54-20.76), 2.6% of those receiving SOR (HR, 3.47; 95% CI, 2.46-4.98), and 1% of those receiving CAP, with median time to initiation of 4 months (range, 1-35 months). A total of 14,468 patients were eligible for evaluation of HTN therapy, which was initiated in 21% of SUN recipients (HR, 4.91; 95% CI, 4.19-5.74), 14% of SOR recipients (HR, 3.25; 95% CI, 2.69-3.91), and 5% of CAP recipients, with median time to initiation of 1 month (range, 1-18 months) for SOR and 2 months (range, 1-25 months) for SUN.

CONCLUSION: SUN and SOR significantly increased the risk for clinically relevant hypothyroidism; the risk was at least 4 times greater with SUN than with SOR. Patients receiving SUN and SOR had a similar elevated risk for clinically relevant HTN. These data provide robust measures of the incidence and time to onset of these clinically actionable adverse events. The Oncologist 2017;22:208-212 Implications for Practice: The side effect profiles for novel therapies are typically used to create monitoring and management recommendations using clinical trial data from patient populations that may not represent those seen in standard clinical practice. This analysis using a large pharmacy claims database better reflects typical patients treated with sorafenib or sunitinib outside of a clinical trial. The findings of increased need for thyroid replacement in patients receiving sunitinib compared with sorafenib and a similar increase in need for hypertension therapy with both agents can be used to form clinically relevant monitoring recommendations for these agents.