**9. Quality of life in patients with renal cell carcinoma receiving targeted**

### **9.1. Therapy**

Quality of life (QoL) has been evaluated in a series of trials of patients taking novel targeted agents for RCC. Questionnaires used have included the Functional Assessment of Cancer Therapy-General (FACT-G), the FACT Kidney Symptom Index-15 item (FKSI-15), the FACT-Kidney Symptom Index-Disease related Symptoms (FKSI-DRS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 and the Euro QOL 5D (Index and Visual Analogue Scale) utility score (EQ-5D) Index.

One of the important outcomes was that newer treatment approaches may be better tolerated with improved QOL compared to the older generation agents. Sunitinib has shown meaningful differences, both in kidney cancer related symptoms and overall QOL over IFN-α. [33] This is not unexpected given the more difficult toxicity profile of sunitinib.

Sorafenib, on the contrary revealed no worst QoL score based on the FACT-G or FKSI-15 undertaken in the TARGET trial. On the other hand, targeted therapies compared to placebo were not revealing worse scores in the QOL questioners. Interestingly, qualitative assessment of one's ability to enjoy life, concerns for well-being, fevers, dyspnea and cough were reported less in the patients on sorafenib. [116]

Pazopanib unexpectedly did not have a clinically different QoL compared with placebo, despite the adverse events that a clinician may expect with pazopanib. [50, 100]

In the AXIS trial where axitinib was compared head-to-head with sorafenib, patient-reported kidney-specific symptom and function assessments were secondary endpoints that were examined. [57] Overall, patients on the axitinib treatment arm reported comparable outcomes to that of sorafenib. The PFS benefit seen by axitinib is associated with a delay in worsening of the composite endpoint of advanced RCC symptoms, progression, or death with sorafenib. [57]

PSICES is a small but important randomized trial comparing patient's preference for pazopa‐ nib or sunitinib for first-line treatment of metastatic RCC. The rationale of this trial was to select the more tolerable agent with the recent approval of numerous TKIs as front-line agents. [117] One hundred and sixty nine patients with metastatic RCC were randomly assigned to blinded treatment of pazopanib for 10 weeks with a wash out prior to 50mg of sunitinib for 10 weeks, and vice versa (4 weeks of sunitinib followed by 2 weeks break before 10 weeks of pazopanib). Fifty four and sixty patients first received pazopanib and sunitinib respectively. The patience preference when assessed at 22 weeks revealed 70% of patients preferred pazopanib, 22% preferred sunitinib, and 8% expressed no preference. The magnitude of difference was 49.3% between pazopanib and sunitinib. Fewer patients received pazopanib required a dose reduc‐ tion (13% vs. 20%), prematurely discontinued treatment during the first study period (14% vs. 8%), or prematurely discontinued treatment during the second period (15% vs. 31%). [117, 118]
