Exploratory analysis of the influence of nephrectomy status on temsirolimus efficacy in patients with advanced renal cell carcinoma and poor-risk features

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5050 Background: Temsirolimus (TEMSR), a novel inhibitor of the mammalian target of rapamycin, has demonstrated significantly longer overall survival (OS) (P=.008) and progression-free survival (PFS) (P<.001) vs interferon alfa (IFN) in patients with previously untreated advanced renal cell carcinoma (RCC) and poor-risk features (Hudes et al., NEJM 2007;356:2271). In poor-risk populations, a high percentage of patients do not have nephrectomy prior to systemic treatment. This retrospective subgroup analysis evaluated the influence of prior nephrectomy on outcomes in patients treated with TEMSR or IFN. Methods: Patients received IFN 3 million units [MU] subcutaneously 3x weekly, escalating to 18 MU, or TEMSR 25-mg intravenous infusion weekly. Kaplan-Meier analysis and a Cox proportional hazards model were used to analyze OS and PFS for the 2 patient subsets (no nephrectomy vs nephrectomy). Results: In each treatment arm, 33% of patients did not receive nephrectomy prior to treatment (IFN, 68/207; TEMSR, 70/209). There was no association between risk factors and nephrectomy status within the 2 treatment arms. Median OS was longer for TEMSR vs IFN (Table), resulting in reduced hazard ratios (HR) for death in both patient subsets (no nephrectomy, HR=0.61 [95% CI, 0.41, 0.91]; nephrectomy, HR=0.84 [95% CI, 0.63, 1.11]). In both subsets, median PFS was longer when treated with TEMSR (no nephrectomy, HR=0.62 [95% CI, 0.43, 0.88]; nephrectomy, HR=0.72 [95% CI, 0.55, 0.93]). Nephrectomy status did not affect temsirolimus efficacy with respect to either OS (P=.20) or PFS (P=.47). Among non-nephrectomized patients, more patients treated with TEMSR showed reductions in primary kidney tumor size than did those treated with IFN (TEMSR, 37/64 [58%]; IFN, 18/59 [31%]). Conclusion: Temsirolimus benefits patients with advanced RCC and poor-prognostic features, regardless of nephrectomy status, and displays activity against primary kidney tumors. No Nephrectomy Nephrectomy IFN TEMSR IFN TEMSR Patients, n (%) 68 (33) 70 (33) 139 (67) 139 (67) Median OS, mo (95% CI) 6.2 (3.8, 8.8) 11.5 (8.5,14.5) 7.8 (6.2, 10.6) 10.4 (8.2, 13.0) OS HR, TEMSR:IFN (95% CI) - 0.61 (0.41, 0.91) - 0.84 (0.63, 1.11) Median PFS, mo (95% CI), independent assessment 2.0 (1.8, 4.3) 5.7 (3.9, 7.5) 3.5 (2.2, 4.3) 5.3 (3.8, 7.1) PFS HR, TEMSR:IFN (95% CI), independent assessment - 0.62 (0.43, 0.88) - 0.72 (0.55, 0.93) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Wyeth Wyeth Wyeth Wyeth