title: Optimisation of the tumour response threshold in patients treated with everolimus for metastatic renal cell carcinoma: analysis of response and progression-free survival in the RECORD-1 study.
abstract: OBJECTIVE
  Objective response as determined by Response Evaluation Criteria in Solid Tumors (RECIST) is low among patients with metastatic renal cell carcinoma (mRCC) treated with targeted agents, despite significantly improved progression-free survival (PFS). A modified response threshold may be more clinically meaningful than RECIST for identifying patients who may derive a PFS benefit from targeted therapy.
  
  
  METHODS
  We performed a retrospective analysis of data from the phase III RECORD-1 trial of everolimus versus placebo in patients with mRCC who had failed sunitinib or sorafenib (ClinicalTrials.gov identifier: NCT00410124). A series of tumour response thresholds, defined by the best change in the sum of the longest tumour diameters (ΔSLD) of target lesions, was evaluated to distinguish 'responders' from 'non-responders' with respect to significant improvement in PFS.
  
  
  RESULTS
  The optimal threshold for determining a response to everolimus was -5% ΔSLD. At this threshold, median PFS was 8.4 months in responders and 5.0 months in non-responders (hazard ratio [HR] 2.4, 95% confidence interval [CI] 1.6-3.7).
  
  
  CONCLUSIONS
  In patients who have failed vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy, everolimus affords superior PFS to placebo, regardless of change in tumour burden. However, a ≥ 5% reduction in SLD is a better predictor of PFS benefit than the classical ≥ 30% reduction used with RECIST.
authors.affiliation: Medical Oncology Department, Georges Pompidou European Hospital, Paris, France. stephane.oudard@egp.aphp.fr
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
authors.forename: Rokhaya
authors.initials: R
authors.lastname: Thiam
authors.forename: Laure S
authors.initials: LS
authors.lastname: Fournier
authors.forename: Jacques
authors.initials: J
authors.lastname: Medioni
authors.forename: Michele
authors.initials: M
authors.lastname: Lamuraglia
authors.forename: Florian
authors.initials: F
authors.lastname: Scotte
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fabre
authors.forename: Dennis
authors.initials: D
authors.lastname: Kim
authors.forename: Euloge
authors.initials: E
authors.lastname: Kpamegan
authors.forename: Ashok
authors.initials: A
authors.lastname: Panneerselvam
authors.forename: Charles A
authors.initials: CA
authors.lastname: Cuenod
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018572:Disease-Free Survival; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy*; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus