The results of an innovative clinical trial have demonstrated significant preferences among both patients and physicians for pazopanib over sunitinib for treatment of metastatic renal cell carcinoma (mRCC).

A range of tyrosine kinase inhibitors is now approved for mRCC therapy, and the similar efficacies and safety profiles of these drugs means that alternative discriminatory factors are required. The similarities between pazopanib and sunitinib, both of which are approved by the FDA as first-line treatments, have now been exploited in the design of a crossover clinical trial.

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169 patients with no previous tyrosine kinase inhibitor treatment were randomly allocated to receive pazopanib in Period 1 (800 mg per day for 10 weeks), a 2-week washout and then sunitinib in Period 2 (50 mg per day, 4 weeks on, 2 weeks off, 4 weeks on), or the reverse (sunitinib, washout, pazopanib). Patients and physicians were blinded to the order of treatment. A questionnaire at the end of the 12-week study period asked patients if they would prefer to continue treatment with the drug administered in Period 1 or Period 2, and assessed the factors influencing their decisions. 114 patients met the criteria for the primary analysis (exposure to both drugs, no disease progression before Period 2, and questionnaire completion). In this group, 70% expressed a preference for pazopanib, with better quality of life the most commonly cited reason for this decision. 22% chose sunitinib, and 8% had no preference. A preference was seen for the treatment given in Period 1 (54%) compared with Period 2 (38%), but it did not affect the overall analysis because of the reciprocal design of the treatment regimen.

Physicians were also questioned, prior to unblinding of the trial, and they too favoured pazopanib (61%) over sunitinib (22%), taking into account the patients' preferences, tumour assessments, apparent drug toxicities and lab test results.

Further work is needed to demonstrate unequivocally the safety and efficacy equivalence of these drugs, the effects of combination therapies and order of treatment in different groups of patients. However, the introduction of preference data further informs physicians and patients. These choices could reveal subtle differences in tolerability that are not captured by adverse event reporting.