title: An international expanded-access programme of everolimus: addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy.
abstract: OBJECTIVE
  The RECORD-1 trial established the clinical benefit of everolimus in patients with metastatic renal cell carcinoma (mRCC) after failure of initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. The REACT (RAD001 Expanded Access Clinical Trial in RCC) study was initiated to address an unmet medical need by providing everolimus prior to commercial availability, and also to further assess the safety and efficacy of everolimus in patients with VEGFr-TKI-refractory mRCC.
  
  
  METHODS
  REACT (Clinicaltrials.gov: NCT00655252) was a global, open-label, expanded-access programme in patients with mRCC who were intolerant of, or who had progressed on or after stopping treatment with, any available VEGFr-TKI therapy. Patients received everolimus 10mg once daily, with dose and schedule modifications allowed for toxicity. Patients were closely monitored for the development of serious and grades 3/4 adverse events (AEs). Response was assessed by RECIST every 3months for the first year and every 6months thereafter.
  
  
  RESULTS
  A total of 1367 patients were enroled. Safety findings and tumour responses were consistent with those observed in RECORD-1, with no new safety issues identified. The most commonly reported serious AEs were dyspnoea (5.0%), pneumonia (4.7%) and anaemia (4.1%), and the most commonly reported grades 3/4 AEs were anaemia (13.4%), fatigue (6.7%) and dyspnoea (6.5%). Best overall response was stable disease in 51.6% and partial response in 1.7% of patients. Median everolimus treatment duration was 14weeks.
  
  
  CONCLUSIONS
  Everolimus is well tolerated in patients with mRCC and demonstrates a favourable risk-benefit ratio.
authors.affiliation: Clinic for Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Medical School Hannover, Hannover, Germany. gruenwald.viktor@mh-hannover.de
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Sevil E
authors.initials: SE
authors.lastname: Bavbek
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Machiels
authors.forename: Se-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: James
authors.initials: J
authors.lastname: Larkin
authors.forename: Petri
authors.initials: P
authors.lastname: Bono
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Daniel
authors.initials: D
authors.lastname: Castellano
authors.forename: Christian U
authors.initials: CU
authors.lastname: Blank
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Knox
authors.forename: Robert
authors.initials: R
authors.lastname: Hawkins
authors.forename: Oezlem
authors.initials: O
authors.lastname: Anak
authors.forename: Marianne
authors.initials: M
authors.lastname: Rosamilia
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Booth
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Pirotta
authors.forename: István
authors.initials: I
authors.lastname: Bodrogi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000556:secondary; D000068338:Everolimus; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D000068338:Everolimus; D040262:Receptors, Vascular Endothelial Growth Factor; D020123:Sirolimus