1769 A PHASE I TRIAL OF VEGFR1 PEPTIDE VACCINES FOR PATIENTS WITH METASTATIC RENAL CELL CARCINOMA

e710

THE JOURNAL OF UROLOGY姞

had intermediate risk disease. CN was performed in 46 (71%) patients. The commonest reason for not performing surgery was disease progression 13 (20%). The median PFS and OS for the cohort was 7 months (95% CI 6 –11 months) and 15 months (95%CI: 10-NA). Fourteen (30%) patients had progression of disease during the treatment break for surgery, 9 of whom achieved further clincal benifit with further sunitinib. The OS for patients with intermediate and poor risk disease was 26 months (11-not reached(NR) months) and 8 months (4-NR months) respectively. The MSKCC poor risk patients fell into 2 groups, those with progressive metastasis who did not undergo surgery (55%) as opposed to a subgroup who obtained clinical benefit with therapy and went on to have CN (45%). These patients had an improved outcome compared to those with primary refractory disease (median OS 6 vs 12 months). Neither a reduction in the size of the primary tumour (above median: 14%) or increased necrosis at surgery (⬎50%) correlated with outcome (HR 1.8 [0.89 – 4.06] and HR 1.68 HR 0.64 – 4.39] respectively). CONCLUSIONS: The outcome of patients with MSKCC intermediate risk treated with sunitinib prior to CN is encouraging and consistent with results seen in the phase III trial sunitinib versus interferon in which most patients had initial nephrectomy, most of them with metachronous mRCC. The role of surgery in the poor risk population remains unclear. It may be useful in those who have clinical benefit with upfront sunitinib. Source of Funding: Both trials were supported by a research grant from Pfizer

1769 A PHASE I TRIAL OF VEGFR1 PEPTIDE VACCINES FOR PATIENTS WITH METASTATIC RENAL CELL CARCINOMA Hirotsugu Uemura*, Marco De Velasco, Kazuhiro Yoshimura, Masahiro Nozawa, Takafumi Minami, Osaka-Sayama, Japan INTRODUCTION AND OBJECTIVES: It has been shown that anti-angiogenesis targeted therapy with receptor tyrosine kinase inhibitors or mTOR inhibitors is suitable for metastatic renal cell carcinoma (mRCC). Anti-angiogenic cancer vaccines, R1-1084 (SYGVLLWEI; HLA-A2402 restricted) and R1-770 (TLFWLLLTL; HLA-A0201 restricted) are epitope peptides derived from human vascular endothelial growth factor receptor 1 (VEGFR1), and have been shown to induce specific CTL responses in various malignancies. To assess toxicity, immunological response and tumor evolution, a phase-I trial was carried out in patients with treatment-refractory mRCC. METHODS: A total of 18 mRCC patients positive for human leukocyte antigen (HLA)-A2402 and/or A0201 were enrolled in this study. Nine patients for each HLA typing vaccine were divided into 3 groups and were injected subcutaneously in a dose-escalation manner (0.5mg, 1mg, 3mg) with each HLA-restricted VEGFR1 peptide. Vaccination schedule included 4 subcutaneous weekly injections. Thereafter, patients without major adverse events who required other treatments received additional vaccinations with increasing doses up to 3 mg at two-week intervals. Toxicity was assessed every two weeks and immunological responses using ELISPOT assay and clinical outcomes using CT scanning were evaluated every three months. RESULTS: Peptide vaccinations were well tolerated with no major adverse events, Augmentation of peptide-specific CTLs was observed in approximately 80 % of the patients, and serial increase of specific CTL responses was observed thereafter. One patient showed partial response and maintained for 16 months. 5 showed stable disease for more than 6 months. At the time of the analysis, median progression free survival was 8 months (from 24 to 626 days), and 11 patients died and 7 remained alive with median follow up of 16 months. CONCLUSIONS: These findings suggest that VEGFR1 peptide vaccines are safe and applicable for mRCC patients. Source of Funding: None

Vol. 185, No. 4S, Supplement, Tuesday, May 17, 2011

1770 CANCER-SPECIFIC SURVIVAL OUTCOMES OF SUNITINIB TREATMENT IN UISS RISK-STRATIFIED METASTATIC RCC PATIENTS Edward Rampersaud*, Tobias Klatte, Frederic Pouliot, David Li, Christine Anterasian, Nazy Zomorodian, Fairooz Kabbinavar, Los Angeles, CA; David Miller, Ann Arbor, MI; Arie Belldegrun, Allan Pantuck, Los Angeles, CA INTRODUCTION AND OBJECTIVES: Prior to the advent of targeted therapies, immunotherapy such as interleukin-2 (IL-2) served as the best available therapy for patients with metastatic kidney cancer. In addition to better tolerability, newer “targeted” treatment options should ideally provide similar or better survival benefits as those achieved with aggressive surgical resection and immunotherapy. We therefore sought to determine how patients treated with sunitinib fared compared to immunotherapy using a large mature cohort of patients treated at a single institution as a benchmark. METHODS: A prospective database including clinical and pathological variables for 1683 patients with RCC was queried. 305 IL-2 treated patients and 51 sunitinib treated patients with metastatic RCC treated in the first-line setting following cytoreductive nephrectomy were identified and stratified using the UCLA Integrated Staging System (UISS) into low-, moderate-, and high-risk groups, and treatment response and disease specific survival (DSS) were assessed. RESULTS: Overall median survival for the entire cohort was 21.5 months in IL-2 treated patients and 19.3 months in sunitinib treated patients (p⫽0.7693). When stratified by UISS risk group, similar survival outcomes were observed between the two treatment groups: low risk (39.7 months vs. not reached, p⫽0.2940), intermediate risk (20.9 vs. 17.7 months, p⫽0.5383), and high risk (10.5 vs. 7.6 months, p⫽0.2993). Patients treated with IL-2 group demonstrated a 7.3% complete response (CR) rate whereas there were no CRs following treatment with sunitinib (p⬍0.001). Clinical benefit (CR⫹ PR ⫹ SD) rate was 55% for IL-2 compared to 84% for sunitinib. Survival in those having stable disease following IL-2 was 31.6 months versus 24.8 months after (p⫽0.007). Excluding non-responders, median survival for IL-2 patients (n⫽167) was 36 months compared to 26 months for sunitinib patients (n⫽37) (p⫽0.06). CONCLUSIONS: Targeted agents have proven attractive due to their relative ease of administration. At UCLA, patients treated with sunitinib for metastatic RCC more frequently achieved a clinical benefit than those treated with IL-2, yet overall survival between the two groups was similar. Benefit in treatment response, however, was at the expense of complete responses and required a trade-off of acute for chronic toxicities. Excluding non-responders, IL-2 related survival exceeded that of sunitinib by 10 months. As our ability to select patients likely to respond to IL-2 improves, a substantial number of patients remain good candidates for IL-2 based therapy. Source of Funding: None

1771 THE IMPACT OF TARGETED MOLECULAR THERAPIES ON THE LEVEL OF RENAL CELL CARCINOMA VENA CAVAL TUMOR THROMBUS Nicholas Cost*, Dallas, TX; Scott Delacroix, Houston, TX; Joshua Sleeper, Paul Smith, Ramy Youssef, Dallas, TX; Brian Chapin, Jose Karam, Stephen Culp, E. Jason Abel, Houston, TX; James Brugarolas, Ganesh Raj, Arthur Sagalowsky, Dallas, TX; Christopher Wood, Houston, TX; Vitaly Margulis, Dallas, TX INTRODUCTION AND OBJECTIVES: Tyrosine kinase inhibitors (TKIs) have demonstrated activity in RCC by reduction of the size of primary tumors and metastases. In this study, we assessed treatment effect of TKIs on IVC tumor thrombi. METHODS: A multi-institutional database of patients treated with TKIs with in-situ primary RCC was reviewed, defining the thrombus level as: I ⫽ Renal Vein, II ⫽ IVC below hepatic veins, III ⫽ Intra-