Background: In the INTORSECT trial, not progression-free (PFS), but overall survival (OS) was higher with sorafenib vs. temsirolimus in 2^nd setting after 1^st sunitinib therapy in mRCC pts. Here, we compare the PFS and OS between any VEGF TKI and mTOR inhibitors (mTORi) in 2^nd setting in mRCC after progression on 1^st VEGF TKI. Methods: Pts were identified from two institutional databases. Survival estimates of PFS and OS were assessed from initiation of 2^nd therapy by Kaplan-Meier methodology and stratified by the median PFS of the 1^st therapy. Results: Of 125 pts treated with a 1^st VEGFR-TKI, 46 received a 2^nd VEGFR-TKI (37%) and 79 received a 2^nd mTORi (63%). Baseline variables such as age, race, gender, histology, MSKCC and IMDC criteria did not differ by 2^nd therapy (Table). Table presents survival estimates in months (mos) by 2^nd therapy. Conclusions: Improved PFS (7.4 vs 4.5 mos, p= 0.026), and a trend for improved OS was observed with 2^nd line VEGFR TKI vs mTORi. Improved PFS was more pronounced with 2^nd VEGFR TKI if 1^stVEFGR TKI usage >8 mos (11.3 vs 5.1 mos, p=0.009), suggesting continued VEGF inhibition may be a pertinent strategy in this subset of patients.

*SBP and DDS: Equal contribution.