BACKGROUND:A relevant percentage of patients with metastatic renal cell carcinoma develop intolerance to vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFr-TKIs) and require careful selection of subsequent treatment.
This retrospective analysis evaluated the safety and efficacy of everolimus in patients enrolled in the phase-III RECORD-1 trial who discontinued previous VEGFr-TKI therapy because of toxicity.
METHODS: Patients with an adverse event (AE) as their primary reason for discontinuation of previous VEGFr-TKI therapy were included. Median progression-free survival (PFS) for VEGFr-TKI-intolerant patients in each arm was estimated using the Kaplan-Meier method, and effect on PFS (hazard ratio (HR)) was calculated using the Cox proportional hazard model.
RESULTS: In VEGFr-TKI-intolerant patients (n=58, 14%), median PFS was 5.4 months with everolimus and 1.9 months with placebo (HR: 0.32; P=0.004). In sunitinib-intolerant patients (n=26), median PFS was 5.1 months with everolimus and 2.8 months with placebo (HR: 0.28; P=0.033). Grade 3/4 AEs reported with everolimus in VEGFr-TKI-intolerant patients included infections (16%), fatigue (7%) and stomatitis (4%). The toxicity profile of everolimus was similar in the VEGFr-TKI-intolerant and overall study populations.
CONCLUSION: Everolimus is well tolerated and efficacious with no increased toxicity in patients intolerant to VEGFr-TKI therapy.
Bracarda S, Hutson TE, Porta C, Figlin RA, Calvo E, Grünwald V, Ravaud A, Motzer R, Kim D, Anak O, Panneerselvam A, Escudier B. Are you the author?
Ospedale San Donato USL8, Istituto Toscano Tumori, Arezzo, Italy.
Reference: Br J Cancer. 2012 Apr 24;106(9):1475-80.