Abstract only 4544^ Background: In non-clear cell renal cell carcinoma (ncRCC), the efficacy of VEGF tyrosine kinase inhibitor (TKI) is controversial. In the while, a mTOR inhibitor, temsirolimus showed a promising efficacy in ncRCC patients in ARCC trial. Hence, we investigated the role of everolimus in ncRCC with this phase II trial. Methods: ncRCC patients received everolimus 10 mg once daily until disease progression or unacceptable toxicity. We included patients who had received VEGF TKI previously, while excluded patients who received previous mTOR inhibitor. The primary end point was progression free survival (PFS). Results: A total of 49 patients were enrolled from 5 centers. Their median age was 57 years (range 24-75 years) and male to female ratio was 37:12. Histology of the patients included papillary (n=29), chromophobe (n=8), collecting duct (n=2), sarcomatoid (n=4), and unclassifiable (n=6) RCC. Twenty-three patients had been treated with VEGF-TKI prior to the study enrollment. Among 49 patients, 46 patients underwent radiologic response assessment after everolimus treatment. Partial response was observed in 5 patients (10.2%) and stable disease in 25 patients (51.0%). Diseases of 16 patients (32.7%) progressed despite of everolimus administration. Histology of 5 patients who showed objective response to everolimus included chromophobe carcinoma (n=2), papillary carcinoma (n=2) and unclassifiable carcinoma (n=1). During the study period, 34 patients experienced PFS events and median PFS was 5.2 months. Patients with chromophobe histology showed longer PFS than patients with the other histologies (median PFS 18.8 months vs. 3.5 months, p=0.027). Estimated median PFS were not significantly different between patients VEGF-TKI treatment and patients without previous VEGF-TKI treatment (median PFS 7.1 vs. 3.7 months, p=0.110). Toxicity profiles were commensurable with previous reports. Conclusions: Everolimus shows considerable efficacy in ncRCC. Patients with chromophobe histology might earn benefit from everolimus treatment especially. Previous treatment with VEGF-TKI seems not to significantly influence outcome of everolimus therapy in these patients. (ClinicalTrials.gov number, NCT00830895)