Disease-Free Survival In Patients At Highest Risk Of Recurrent Renal Cell Carcinoma In S-Trac.

4565 Background: Sunitinib (SU) is FDA-approved for adjuvant treatment of patients (pts) at high risk (≥T3, any Fuhrman grade and/or nodal involvement [N+]) of recurrent renal cell carcinoma (RCC) post nephrectomy, based on the phase 3 S-TRAC trial that showed significant improvement with SU vs placebo (PBO) in disease-free survival (DFS) based on blinded independent central review (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.59–0.98; P= 0.03). The definition of high risk in S-TRAC included both objective (T stage and Fuhrman grade) and more subjective (pre-nephrectomy Eastern Cooperative Oncology Group performance status [ECOG PS]) prognostic parameters. To delineate the highest risk pts from S-TRAC purely based on objective parameters, we performed an additional analysis classifying pts at highest risk of recurrence post nephrectomy, defined as T3 and Fuhrman grade > 2 or T4 or N+ and any T. Methods: DFS analyses were conducted using Cox proportional hazard model. Results: In S-TRAC, 398 (65%) patients were classified at highest risk. The results indicated a treatment benefit in DFS by independent review for SU vs PBO in this highest risk group (HR 0.73; 95% CI 0.54–0.97; P= 0.03), consistent with the HR for DFS previously reported in the S-TRAC trial for the T3 higher (HR 0.74; 95% CI 0.55–0.99; P= 0.04) group defined as T3 with Fuhrman grade ≥2 and ECOG PS ≥1 or T4 with any ECOG PS or N+ with any T, any ECOG PS, as well as with the overall population. Safety data did not identify major differences between the highest risk group vs overall S-TRAC pts. Incidence of key adverse events with SU was similar in highest risk group vs overall study pts (diarrhea: 58.2% vs 56.9%; palmar-plantar erythrodysesthesia syndrome: 51.5% vs 50.3%; hypertension: 35.7% vs 36.9%; fatigue: 37.2% vs 36.6%; hypothyroidism: 15.3% vs 18.3%). Conclusions: The clinically meaningful treatment benefit observed in pts at highest risk of recurrence and the overall S-TRAC population, together with a consistent safety profile between these groups, support the favorable benefit/risk assessment of SU as an adjuvant treatment option for pts with RCC at high risk of recurrence post nephrectomy. Clinical trial information: NCT00375674.