The use of tumor growth rate (TGR) in evaluating sorafenib and everolimus treatment in mRCC patients: An integrated analysis of the TARGET and RECORD phase III trials data.

Abstract

4540 Background: RECIST criteria may not be sufficient to evaluate targeted therapies in mRCC. TGR includes the time between each evaluation and is expected to overcome some of the RECIST pitfalls. How TGR is modified under targeted therapies and how it correlates with outcome in mRCC remains unknown. Methods: Medical records from all patients (pts) prospectively treated at Institut Gustave Roussy (IGR) in the TARGET (n=84) and in the RECORD (n= 52) phase III trials were extracted. Results were subsequently validated in the entire TARGET cohort (TARGET) (n=902). TGR was computed by dividing tumor shrinkage by the time between the two related evaluations (% RECIST x 100 / days). Typical treatment periods were assessed: BEFORE treatment (wash-out), UNDER treatment (first cycle), at PROGRESSION (pts still receiving the drug) and AFTER treatment interruption (wash-out). Results: As compared to placebo, TGR UNDER was significantly decreased following sorafenib (-23.6 vs. 20 (IGR) and -19 vs. 22 (TARGET)) and everolimus (-5.2 vs. 30 (IGR)). The great majority of pts (IGR) had a decrease in the TGR UNDER vs. BEFORE, regardless of the RECIST evaluation, both with sorafenib (28/29) or everolimus (36/37). TGR AFTER sorafenib or everolimus interruption was significantly higher than TGR at PROGRESSION in both settings (IGR) (14.6 vs. 31 and 17.9 vs. 32.1 respectively). No significant difference was observed between TGR AFTER vs. BEFORE either in sorafenib or in everolimus pts (IGR). High TGR UNDER is associated with poor progression free survival (HR= 2.6) and overall survival (HR= 2.3) in sorafenib-treated pts (multivariate analysis, trained in IGR and validated in TARGET cohorts) and with poor overall survival in everolimus-treated pts (IGR)(HR= 1.2). Conclusions: Adding TGR assessment in mRCC unravels interesting traits that make it potentially adaptable for clinical practice: (i) better evaluation of the tumor response, regardless of RECIST criteria, (ii) independent prognosis value, (iii) it suggests that maintaining sorafenib or everolimus after disease progression might benefit to patients and should be prospectively evaluated.