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Nadal R , Amin A , Geynisman DM , Voss MH , Weinstock M , Doyle J , Zhang Z , Viudez A , Plimack ER , McDermott DF , Motzer R , Rini B , Hammers HJ
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
Ann Oncol. 2016 Jul;27(7) :1304-11
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BACKGROUND: Emerging agents blocking the PD-1 pathway show activity in metastatic clear cell renal cell carcinoma (mRCC). The aim of this study was to evaluate the efficacy and safety of vascular endothelial growth factor (VEGF)/ VEGF receptor (VEGFR) - tyrosine kinase inhibitor (TKI) therapy after programmed cell death 1 (PD-1) inhibition. METHODS: Patients with mRCC treated with anti-PD-1 antibody (aPD-1) monotherapy or in combination (with VEGFR-TKI or ipilumumab) that subsequently received VEGFR-TKI, were retrospectively reviewed. The efficacy end points were objective response rate (ORR) and progression-free survival (PFS) stratified by type of prior PD-1 regimen. Safety by type and PD-1 exposure was also evaluated. RESULTS: Seventy patients were included. Forty-nine patients received prior therapy with immune checkpoint inhibitors (CPI) alone and 21 had combination therapy of aPD-1 and VEGFR-TKI. Overall, ORR to VEGFR-TKI after PD-1 inhibition was 28% (19/68) and the median PFS was 6.4 months (mo) (4.3-9.5). ORR to VEGFR-TKI after aPD-1 in combination with VEGFR-TKI was lower than in patients treated with VEGFR-TKI after CPI alone (ORR 10% versus 36%, p=0.039). In the multivariable analysis, patient treated with prior CPI 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 (AEs) were asthenia, hypertension and diarrhea. CONCLUSIONS: The efficacy and safety of VEGFR-TKIs after PD-1 inhibition was demonstrated in this retrospective study. The response rate was lower and the mPFS shorter in those patients who received prior PD-1 in combination with VEGFR-TKI. PD-1 exposure does not seem to significantly influence the safety of subsequent VEGFR-TKI treatment.
1569-8041 Nadal, R Amin, A Geynisman, D M Voss, M H Weinstock, M Doyle, J Zhang, Z Viudez, A Plimack, E R McDermott, D F Motzer, R Rini, B Hammers, H J Journal article Ann Oncol. 2016 Apr 7. pii: mdw160.