Sunitinib (SU) Dosing Schedule and Data Collection Timepoints: Impact on Quality of Life (QOL) Outcomes in Metastatic Renal Cell Carcinoma (MRCC)

ABSTRACT Background In a randomized phase III trial, SU was associated with superior QoL compared with interferon-alfa (IFN). Here, we report implications related to the timing of collection of QoL data as it relates to SU-approved dosing in mRCC (4 weeks on treatment, 2 weeks off treatment; Schedule 4/2) and the extent to which such timing affects reported outcomes. Methods 750 treatment-naive patients with mRCC were randomized 1:1 to receive SU 50 mg orally once daily on Schedule 4/2 or IFN 9 MU subcutaneously thrice weekly. QoL measures included FACT-G, FKSI-15, FKSI-DRS, EQ-5D, and EQ-VAS. Higher scores indicated better outcomes (better QoL or fewer symptoms). Patients completed QoL questionnaires on Days 1 and 28 of each cycle, up to a maximum of 30 cycles. SU data were analyzed to describe how the timing of QoL collection may affect results. Random coefficients mixed-effects models were used. Results Data were used from all assessments collected (Days 1 and 28 at every cycle). The model indicated that QoL results based on Day 28 collection were consistently and statistically worse (lower QoL scores) than results based on Day 1 (table). Based on a comparison with previously reported between-arm differences with SU vs. IFN, such variation could potentially diminish or increase the observed treatment effect by 38% to 62%. Conclusions To account for overall patient QoL experience on therapy, in this case, SU on Schedule 4/2, careful consideration must be given to the timing of QoL data collection. For SU in mRCC, QoL data should be collected both on and off treatment within a cycle. If QoL data are collected at only the last or first dose, scores will be overly negative or positive, respectively. Hence, if QoL data are collected at only a single timepoint within a cycle, it may not represent the full extent of QoL as experienced by patients on SU and may lead to misinterpretation of the true QoL outcomes. Model means of QoL endpoints with SU by assessment day Endpoint Day 1 (i.e., after 2 weeks off drug) Day 28 (i.e., after 4 weeks on drug) Difference between Day 1 and Day 28 P value Difference between Day 1 and Day 28 as percentage of treatment effect * (SU vs. IFN) FKSI-15 46.3 44.3 2.0 50% FKSI-DRS 29.9 28.9 1.0 43% FACT-G total score 82.9 80.2 2.7 40% EQ-5D Index 0.76 0.73 0.03 62% EQ-VAS 76.1 73.2 2.9 38% FACT-G, Functional Assessment of Cancer Therapy–General; FKSI-15, FACT-Kidney Symptom Index-15; FKSI-DRS, FKSI-Disease-Related Symptoms; EQ-5D, EuroQol 5-dimension; EQ-VAS, EQ visual analog scale. * Based on unrounded values of the Day 1–Day 28 difference and the between-arm difference in model means of endpoints across all available post-baseline observations (Cella D, et al. Br J Cancer 2010;102:658–64). Disclosure A. Bushmakin: Employed by Pfizer as an Assiate Director of Biostatistics and holds Pfizer stock. J.C. Cappelleri: Employed with Pfizer as a Senior Director of Biostatistics and holds Pfizer stock. B. Korytowsky: Employed by Pfizer as a Director of Health Economics Outcomes Research and holds Pfizer stock. R. Sandin: Employed by Pfizer as a Director and holds Pfizer Stock. E. Matczak: Employed by Pfizer as a Medical Director, holds Pfizer stock, and receives honoraria from Pfizer. D. Cella: Advisory relationship with Pfizer. Research funding from Pfizer.