520 Background: Targeted therapy has improved clinical outcomes in metastatic renal cell carcinoma (mRCC). However, patients with unfavorable performance status are often under-represented in clinical trials of mRCC. Methods: Patients with mRCC (clear or non-clear cell) and ECOG PS >2 were included in retrospective study.Primary objective of this study was to evaluate the overall duration of targeted therapy (ODT). ODT was defined as time from initiation of first-line therapy until the end of last-line therapy. Results: 79 patients with ECOG PS >2 (median age, 60 [48-70]; male, 73%; clear-cell RCC, 95%; MSKCC intermediate/poor risk, 97%/3%) were treated with sunitinib (77%), sorafenib (23%), everolimus (20%), bevacizumab + IFN (15%), pazopanib (4%), temsirolimus (2.5%) of which 55 (70%) received only first-line therapy, 24 (30%) received 2 lines, and 9 (11%) received 3 lines of therapy. The median ODT was 9.8 months (95% CI 6–13.6). The median time to progression of patients that received 1, 2 or 3 lines was 7.1, 5.9, and 6.3 months, respectively. One patient showed complete response and 2 patients had partial responses during first-line therapy, 2 patients had partial responses during second-line therapy, and 1 patient had partial response after 2 months of third-line therapy. Among the patients who discontinued treatment, disease progression was the most common reason for discontinuation. There was no unexpected serious toxicity. Conclusions: mRCC patients with unfavorable performance status could be treated with targeted therapy during 9.8 months.