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Metastatic renal cell carcinoma (mRCC) is usually a lethal disease. The introduction of tyrosine kinase inhibitors (TKIs) was a milestone in the treatment of advanced and mRCC. Several randomized, controlled trials have improved our understanding of treatment algorithms and the choice of drugs in the treatment cascade. However, several questions remain, including the selection of one drug over another in the case of equivalent availability. Based on Level 1 Evidence, both sunitinib and pazopanib are FDA approved for first-line mRCC treatment. The COMPARZ trial demonstrated that both drugs have similar efficacy, but the investigators reported differences in health-related quality of life (HRQoL), favouring pazopanib over sunitinib for 11 of 14 comparisons [1].
In the selected JCO article, Escudier et al. [2] now report thorough results of a randomized, controlled, doubleblind, cross-over trial (PISCES) that evaluated patient preference for pazopanib versus sunitinib in patients with mRCC. TKI-naïve patients were randomly assigned to receive either pazopanib 800 mg per day for 10 weeks followed by a 2-week washout phase (period 1), and then sunitinib 50 mg (4 weeks on, 2 weeks off, 4 weeks on) for 10 weeks (period 2), or the reverse sequence. A questionnaire that measured patient preference for a specific treatment at the end of the two treatment periods was the basis for the primary end point. Physicians were also asked to state their preference for a patient’s further treatment before unblinding. Of importance, dose reductions for adverse events were permitted.
The investigators found that more patients preferred pazopanib (70%) over sunitinib (22%), due to less fatigue, whereas those preferring sunitinib reported less diarrhea. Interestingly, physician preference was consistent with patient preference, with more physicians preferring to continue their patients on pazopanib (61%) than on sunitinib (22%), although the authors reported no reasons for these preferences.
In summary, the results of the COMPARZ and PISCES studies [1, 2] may suggest that every TKI-naïve patient with mRCC should preferably be treated with pazopanib rather than sunitinib. There is no doubt that HRQoL is an essential parametre that will affect decision making regarding oncological therapy strategies [3]. However, we should be aware that treatment decisions are more complicated than just selecting one drug over another according to individual preferences. Patients’ comorbidities, risk profiles, and tumour features are of greater importance than reported in the PISCES study. In addition, from clinical practice we know that patients’ adaptation to a drug often improves after two cycles, particularly in patients with first-line treatment who have never received any TKI before. Moreover, we know that dose escalation to the maximum dose after starting with a reduced dose as well as a dose reduction in the case of adverse events are associated with improved patient drug tolerability and consequently better HRQoL.
In addition, it is of critical importance that the patients be treated with the most effective drug. In both the COMPARZ and PISCES studies [1, 2], sunitinib performed, although not statistically significant, better than pazopanib in terms of several efficacy parametres. Median progression-free survival was 8.4 months for pazopanib and 9.5 months for sunitinib [1], and, albeit smaller and of shorter duration, there was a 20% progressive disease rate in period 1 for pazopanib versus 11% for sunitinib in the current study [2]. The patient and physician preferences for an individual pharmaceutical drug should be based on unequivocal safety and efficacy, and at least patients’ preferences could potentially have been influenced by disclosure of such data to study participants [4].
Although the PISCES study was a decent endeavour at defining treatment preferences, on the basis of the concerns raised here and by others [4], one should still carefully select the choice of initial treatment, as current data do not provide compelling enough evidence to claim superiority of pazopanib over sunitinib.