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

There is limited data on the efficacy and safety of VEGFR-TKI after PD-1 inhbition. This multi-institutional and retrospective study included 70 patients with metastatic clear renal cell carcinoma (mRCC) enrolled in three prospective trials evaluating aPD-1 therapy. Patients received aPD-1 monotherapy or aPD-1 in combination with VEGFR-TKI or Ipilimumab and subsequently were treated with VEGFR-TKIs. By the Memorial Sloan Kettering Cancer Center prognostic risk group criteria, 30% of the patients were favorable risk, 27.1% were intermediate risk and 27.1% were poor risk. The objective response rate (ORR) for VEGFR -TKI therapy after PD-1 inhibition was 28.4% and the median PFS was of 6.4 months (4.3-9.5). Patient treated with immune checkpoint inhibitors alone were more likely to achieve an objective response than those treated with aPD-1 in combination with VEGFR-TKI (OR=5.38; 95% CI=1.12-26.0, p=0.03). There was a trend toward numerically longer median PFS in the VEGFR-TKI after CPI alone group, 8.4 mo (3.2-12.4) compared to 5.5 mo (2.9-8.3) for those who had VEGFR-TKI after aPD-1 in combination with VEGFR-TKI (p=0.15). The most common adverse events were asthenia, hypertension and diarrhea. Treatment with VEGFR-TKIs has clinical activity and can be done safely after PD-1 inhibition in this selected population of patients with mRCC. ORR with VEGFR-TKIS was significantly lower and a trend towards shorter mPFS was noted in patients who received prior aPD-1 in combination with VEGFR-TKI. PD-1 exposure does not seem to influence the safety of subsequent VEGFR-TKI treatment.

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