Charles Ferté1, Serge Koscielny2, Laurence Albiges3, Laurence Rocher4, Jean-Charles Soria3, Roberto Iacovelli5, Yohann Loriot3, Karim Fizazi3, Bernard Escudier6. 1. 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. 2. INSERM U981, Paris Sud University, Gustave Roussy, Villejuif, France; Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France. 3. Department of Medical Oncology, Gustave Roussy, Villejuif, France; INSERM U981, Paris Sud University, Gustave Roussy, Villejuif, France. 4. Department of Radiology, University Hospital of Bicêtre, Le Kremlin-Bicêtre, France. 5. Department of Medical Oncology, Gustave Roussy, Villejuif, France. 6. Department of Medical Oncology, Gustave Roussy, Villejuif, France; INSERM U981, Paris Sud University, Gustave Roussy, Villejuif, France. Electronic address: escudier@igr.fr.
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. DESIGN, SETTING, AND PARTICIPANTS: 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). INTERVENTION: Sorafenib, everolimus, or placebo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: TGR, RECIST, OS, and PFS rates. RESULTS AND LIMITATIONS: 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.
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. DESIGN, SETTING, AND PARTICIPANTS: 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). INTERVENTION: Sorafenib, everolimus, or placebo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: TGR, RECIST, OS, and PFS rates. RESULTS AND LIMITATIONS: 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: Patrick M Dillon; Gina R Petroni; Bethany J Horton; Christopher A Moskaluk; Paula M Fracasso; Michael G Douvas; Nikole Varhegyi; Snjezana Zaja-Milatovic; Christopher Y Thomas Journal: Clin Cancer Res Date: 2017-04-04 Impact factor: 12.531
Authors: Angela Lamarca; Joakim Crona; Maxime Ronot; Marta Opalinska; Carlos Lopez Lopez; Daniela Pezzutti; Pavan Najran; Luciana Carvhalo; Regis Otaviano Franca Bezerra; Philip Borg; Naik Vietti Violi; Hector Vidal Trueba; Louis de Mestier; Niklaus Schaefer; Anders Sundin; Frederico Costa; Marianne Pavel; Clarisse Dromain Journal: Oncologist Date: 2019-03-25
Authors: Charles Ferté; Marianna Fernandez; Antoine Hollebecque; Serge Koscielny; Antonin Levy; Christophe Massard; Rastislav Balheda; Brian Bot; Carlos Gomez-Roca; Clarisse Dromain; Samy Ammari; Jean-Charles Soria Journal: Clin Cancer Res Date: 2013-11-15 Impact factor: 12.531