title: Tumor growth rate provides useful information to evaluate sorafenib and everolimus treatment in metastatic renal cell carcinoma patients: an integrated analysis of the TARGET and RECORD phase 3 trial data.
abstract: BACKGROUND
  Response Evaluation Criteria in Solid Tumors (RECIST) criteria may not be sufficient to evaluate the response of targeted therapies in metastatic renal cell carcinoma (mRCC). The tumor growth rate (TGR) incorporates the time between evaluations and may be adequate.
  
  
  OBJECTIVE
  To determine how TGR is modified along the treatment sequence and is associated with outcome in mRCC patients.
  
  
  METHODS
  Medical records from all patients prospectively treated at Gustave Roussy (IGR) in the Treatment Approaches in Renal Cancer Global Evaluation Trial (TARGET) (sorafenib vs placebo, n=84) and the RECORD (everolimus vs placebo, n=43) phase 3 trials were analyzed. TGR was computed across clinically relevant periods: BEFORE treatment introduction (wash-out), UNDER (first cycle), at PROGRESSION (last cycle) and AFTER treatment discontinuation (washout). The association between TGR and outcome (overall survival [OS] and progression-free survival [PFS]) was computed in the entire TARGET cohort (n=903).
  
  
  METHODS
  Sorafenib, everolimus, or placebo.
  
  
  METHODS
  TGR, RECIST, OS, and PFS rates.
  
  
  CONCLUSIONS
  Although nearly all the patients (IGR) were classified as stable disease (RECIST) after the first cycle, the great majority of the patients exhibited a decrease in TGR UNDER compared with BEFORE (sorafenib: p<0.00001; everolimus: p<0.00001). In sorafenib-treated but not in everolimus-treated patients (IGR), TGR at PROGRESSION (last cycle) was still lower than TGR BEFORE (washout) (p=0.012), while TGR AFTER progression (washout) was higher than TGR at PROGRESSION (last cycle) (p=0.0012). Higher TGR (first cycle) was associated with worse PFS (hazard ratio [HR]: 3.61; 95% confidence interval [CI], 2.45-5.34) and worse OS (HR: 4.69; 95% CI, 1.54-14.39), independently from the Motzer score and from the treatment arm in the entire TARGET cohort.
  
  
  CONCLUSIONS
  Computing TGR in mRCC patients is simple and provides clinically useful information for mRCC patients: (1) TGR is independently associated with prognosis (PFS, OS), (2) TGR allows for a subtle and quantitative characterization of drug activity at the first evaluation, and (3) TGR reveals clear drug-specific profiles at progression.
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif, France; INSERM U981, Paris Sud University, Gustave Roussy, Villejuif, France; Sage Bionetworks, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Ferté
authors.affiliation: INSERM U981, Paris Sud University, Gustave Roussy, Villejuif, France; Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Koscielny
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif, France; INSERM U981, Paris Sud University, Gustave Roussy, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Albiges
authors.affiliation: Department of Radiology, University Hospital of Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Rocher
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif, France; INSERM U981, Paris Sud University, Gustave Roussy, Villejuif, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif, France.
authors.forename: Roberto
authors.initials: R
authors.lastname: Iacovelli
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif, France; INSERM U981, Paris Sud University, Gustave Roussy, Villejuif, France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Loriot
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif, France; INSERM U981, Paris Sud University, Gustave Roussy, Villejuif, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
authors.affiliation: Department of Medical Oncology, Gustave Roussy, Villejuif, France; INSERM U981, Paris Sud University, Gustave Roussy, Villejuif, France. Electronic address: escudier@igr.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D018572:Disease-Free Survival; D000068338:Everolimus; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011446:Prospective Studies; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077157:Sorafenib; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000068338:Everolimus; D000077157:Sorafenib; D020123:Sirolimus
keywords: Everolimus; Metastatic renal cell carcinoma (mRCC); Prognosis; RECIST; Sorafenib; Tumor growth rate (TGR)