BACKGROUND: Monoclonal antibodies that target the programmed death-1 
(PD-1)/programmed death-ligand 1(PD-L1) pathway have shown antitumour activity 
in metastatic renal cell carcinoma (mRCC) and are currently being developed in 
first-line (in combination) and in previously treated patients. The efficacy 
targeted therapy (TT) after PD-1/PD-L1 blockade is still unknown.
METHODS: Medical records of mRCC patients treated with investigational PD-1 or 
PD-L1 inhibitors at 4 academic institutions were reviewed. Patients who received 
subsequent treatment with TT were selected to collect outcome measures of 
subsequent TT.
RESULTS: Of 99 patients who received PD-1/PD-L1 blockade as part of clinical 
trials, 56 patients have received subsequent therapy: 44 patients received 
vascular endothelial growth factor (VEGF)/vascular endothelial growth factor 
receptor (VEGFR) inhibitors and 12 received mammalian target of rapamycin (mTOR) 
inhibitors as first subsequent TT. Median follow up, from the start of 
subsequent TT was 16.1 months (range: 0.2, 30.6 months). TT post PD-1/PD-L1 
blockade was administered as second-line, third-line or beyond third-line in 9 
(16%), 24 (43%) and 23 patients (41%) respectively. Median time to treatment 
failure on subsequent TT was 6.6 months (range: 0.2+, 23.0). 1-year and 2 year 
overall survival from the initiation of subsequent TT was 58% (95% confidence 
interval (CI): 41-72%) and 36% (95% CI: 18-54%), respectively.
CONCLUSION: Both VEGF/VEGFR and mTOR inhibitors demonstrate antitumour activity 
following PD-1/PD-L1 blockade.