Sunitinib (SU) was FDA-approved for adjuvant treatment of patients (pts) with renal cell carcinoma (RCC) at high risk of recurrence post nephrectomy, based upon a 24% reduction in disease-free survival with up to 1 year of SU treatment vs placebo (PBO) (S-TRAC trial). The analysis of patient-reported outcomes (PRO) data showed a statistically significant difference favoring PBO in most EORTC QLQ-C30 scales, and in the symptoms appetite loss and diarrhea, a clinically meaningful difference (≥ 10 points) favoring PBO was observed. Recognizing that some pts did not tolerate SU early on, with higher discontinuation and dose reduction rates for SU than PBO, we describe a baseline reset analysis to assess the longitudinal PRO profile of pts who were able to tolerate and stay on treatment beyond the first 2 cycles (C).
After censoring the data from C1 and 2, and resetting a new baseline at C 3, the baseline reset analysis described here used the same statistical analysis done for PRO data in S-TRAC. For each scale, comparison of the two treatment arms was carried out using longitudinal repeated measures mixed effect.
Of the 615 pts enrolled in S-TRAC, 580 were included in the PRO analyses. Of these, 506 pts had PRO data at C 3 and were included in this analysis. The longitudinal between treatment comparison resulted in statistically significant differences favoring PBO in 6 of the 15 scales with no clinically meaningful differences (≥10 points) (see Table). The discontinuation rates of the 2 treatment groups were comparable from C 3 onward.Table: 916P
Summary results: EORTC QLQ-C30: Scores between treatment comparison – intent-to-treat population (cycles 3-9)
|Sunitinib (n = 241) Model Estimated Mean||Placebo (n = 265) Model Estimated Mean||Difference (Sunitinib – Placebo)|
|Global Health status/QoL (large values better)||69.87||72.20||-2.32*|
|Functional scales (large values better)|
|Symptom items/scales (large values worse)|
|Nausea and vomiting||6.50||5.30||1.21|
|Appetite loss||12.21||7.74||4.47 *|
A repeated measures longitudinal analysis with an intercept term, and treatment, time, treatment by time, and baseline as covariate over all cycles.*
P < 0.05
P-values not adjusted for multiplicity.
These analyses suggest that for pts who are able to tolerate SU for > 2 cycles (3 months), PRO profiles for SU are similar to PBO pts with similar discontinuation rates. Some pts do not tolerate SU early on in the adjuvant setting, but for the majority who do, long term tolerance may be more acceptable than originally thought.
Clinical trial identification
Legal entity responsible for the study
D.J. George: Honoraria & Consulting: Sanofi, Exelixis, Bayer; Consulting: Merck, Sanofi; Grants: Genentech/Roche, Novartis, Astellas, Celldex, Acerta; Grants & Consulting: Exelixis, Janssen, Pfizer, Innocrin Pharma, BMS. R. Figlin: Funding: Merck, Pfizer, Peloton, Calithera; Consulting fees: Pfizer. R.J. Motzer: Consulting fees: Pfizer, Eisai, Novartis, Exelixis; Clinical trial support to institution: Pfizer, Eisai, Novartis, Bristol-Myers Squibb, Genentech/Roche, Exelixis. M.J. Lechuga Frean, G. Zanotti, H. Bhattacharyya, K. Ramaswamy, L. Deannuntis: Employee of and owns stock in Pfizer. A. Ravaud: Advisory boards: Pfizer, Novartis, GSK, Roche, BMS; Institutional support grants: Pfizer, Novartis; Housing and transportation for meetings and speeches: Pfizer, Novartis, BMS. All other authors have declared no conflicts of interest.