Characterizing fatigue associated with sunitinib (SU) in patients (pts) with metastatic renal cell carcinoma (mRCC).

Abstract

6092 Background: Fatigue is common in cancer pts and associated with use of tyrosine kinase inhibitors (TKIs) such as SU. Limited data exist on the time pattern of fatigue with TKI therapy. Methods: Data from treatment-naïve mRCC pts in SU arms of two clinical trials were analyzed retrospectively. Study 1; 375 pts were randomized to SU 50 mg/d on a 4 weeks-on-2-weeks-off schedule (Schedule 4/2), for up to 30 cycles. Study 2; pts were randomized to SU 50 mg/d Schedule 4/2 (Group 1; n=146) or 37.5 mg/d continuous daily dosing (CDD; Group 2; n=146). In both trials, fatigue was measured with the question to pts: “I feel fatigued” over the past week (5-point rating scale, not at all-very much), and with the provider-rated Common Terminology Criteria for Adverse Events (CTCAE). In addition to descriptive profiles, Study 1 used two modeling approaches; repeated measures model (M1), with time as a categorical predictor; and random intercept-slope model (M2), with time as a continuous predictor. Study 2 calculated mean absolute values of within-cycle rate of change (from one assessment to the next) through the first 6 treatment cycles. Results: In Study 1, representing fatigue across cycles, M1 showed that the initial increase in patient-reported fatigue was worst during Cycle 1; mean values at all subsequent cycles were numerically better. For CTCAE fatigue, M1 showed that all but one of the pair-wise comparisons of the cycle means were not significantly different. M2 showed that the overall trend for patient-reported fatigue and CTCAE fatigue was not statistically different from zero. In Study 2, the mean absolute rate of change for fatigue during 6 treatment cycles was greater for Group 1 (4/2) compared to Group 2 (CDD): 0.042 vs. 0.032, respectively; P=0.003, t-test. Conclusions: In Study 1, pts reported notable fatigue in Cycle 1, which improved or stabilized, thereafter. In Study 2, Schedule 4/2 was associated with more within-cycle fluctuation in fatigue. These findings illustrate how SU-associated fatigue occurs early in therapy and continues with more within-cycle fluctuation associated with 4/2 dosing. This may help patient-clinician communications and interventions that support maintaining effective therapy.