Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are safe and effective after treatment with a programmed cell death 1 (PD-1) inhibitor in patients with metastatic renal cell carcinoma (mRCC), a retrospective study published in the journal Annals of Oncology has shown.1

Because novel agents like nivolumab that block the PD-1 pathway have demonstrated activity in mRCC, researchers sought to evaluate the efficacy and safety of VEGF/VEGFR-TKI therapy following PD-1 inhibition.

For the study, researchers analyzed data from 70 patients with mRCC who were treated with anti-PD-1 antibody monotherapy or in combination, as ipilimumab plus a VEGFR-TKI. Patients were only included if they subsequently received a VEGFR-TKI.

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Researchers found that 49 patients received prior therapy with an immune checkpoint inhibitor alone and 21 had combination therapy with an anti-PD-1 inhibitor and a VEGFR-TKI.

Results showed that the objective response rate to VEGFR-TKI therapy after PD-1 inhibition was 28%. Only 10% of patients who received combination therapy achieved a response compared with 36% of those who received a VEGFR-TKI after checkpoint inhibitor therapy alone (P = .039).

The study demonstrated that patients treated with prior checkpoint inhibitor therapy alone had a higher likelihood of achieving an objective response than those treated with anti-PD-1 inhibitor plus a VEGFR-TKI (OR, 5.38; 95% CI, 1.12 – 26.0; P = .03). There was also a trend toward longer progression-free survival in patients who received a VEGFR-TKI after a checkpoint inhibitor alone as compared with those who received combination therapy.

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In terms of safety, the most frequently reported adverse events with subsequent VEGFR-TKI therapy were asthenia, hypertension, and diarrhea, suggesting that prior PD-1 exposure did not significantly impact that safety of subsequent VEGFR-TKI treatment.


  1. Nadal R, Amin A, Geynisman DM, et al. Safety and clinical activity of vascular endothelial growth factor receptor (VEGFR)- tyrosine kinase inhibitors after programmed cell death 1 inhibitor treatment in patients with metastatic clear cell renal cell carcinoma [published online ahead of print April 7, 2016]. Ann Oncol. doi: 10.1093/annonc/mdw160.