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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) 27:1304-11.
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.
Publication Date: 2016-07-01.
Last updated on Saturday, July 11, 2020