title: Everolimus in metastatic renal cell carcinoma patients intolerant to previous VEGFr-TKI therapy: a RECORD-1 subgroup analysis.
abstract: 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.
  
  
  CONCLUSIONS
  Everolimus is well tolerated and efficacious with no increased toxicity in patients intolerant to VEGFr-TKI therapy.
authors.affiliation: Ospedale San Donato USL8, Istituto Toscano Tumori, Arezzo, Italy. sergio.bracarda@usl8.toscana.it
authors.forename: S
authors.initials: S
authors.lastname: Bracarda
authors.forename: T E
authors.initials: TE
authors.lastname: Hutson
authors.forename: C
authors.initials: C
authors.lastname: Porta
authors.forename: R A
authors.initials: RA
authors.lastname: Figlin
authors.forename: E
authors.initials: E
authors.lastname: Calvo
authors.forename: V
authors.initials: V
authors.lastname: Grünwald
authors.forename: A
authors.initials: A
authors.lastname: Ravaud
authors.forename: R
authors.initials: R
authors.lastname: Motzer
authors.forename: D
authors.initials: D
authors.lastname: Kim
authors.forename: O
authors.initials: O
authors.lastname: Anak
authors.forename: A
authors.initials: A
authors.lastname: Panneerselvam
authors.forename: B
authors.initials: B
authors.lastname: Escudier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D004311:Double-Blind Method; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007390:International Agencies; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D016879:Salvage Therapy; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D000068338:Everolimus; D040262:Receptors, Vascular Endothelial Growth Factor; D020123:Sirolimus