Early Tumor Shrinkage (Ets) As A Predictive And Prognostic Factor In Metastatic Renal Cell Carcinoma (Mrcc).

4551 Background: Tumor shrinkage (TS) has predictive value in mRCC, and early TS has been reported to be associated with prognosis in small series with mRCC, but the optimal cut-off has not been defined. We therefore quantitated the degree of tumor shrinkage at first scan that has predictive or prognostic value in mRCC. Methods: Data from Pfizer-sponsored clinical trials with sunitinib, axitinib, sorafenib, IFN or temsirolimus in mRCC were included for this posthoc analysis (A6181006, A6181034, A6181061, A6181065, A6181110, RTKC-0511-014, A4061032, A4060146, A4061051, 3066K1-304, 3066K1-3311, 3066K1-404). Objective tumor response was captured by protocol-defined tumor imaging according to RECIST. Target lesions were followed for TS. eTS was assessed at first post-baseline scan and analyzed for sensitivity and specifity by receiver-operating characteristic (ROC) analyses to predict response measured by median progression free survival (PFS) or overall survival (OS). Patients were classified as responders if PFS (7 mo.) or OS (20 mo.) were above the median. Results: 4736 pts (71% male) with median age 59 years were identified within the database. Most patients were treatment naïve (67%), had clear cell histology (89%), and favorable performance status (ECOG 0/1: 53/47%). Overall, an eTS of 7% or 8% was identified as the optimal cut-off for prediction of PFS or OS, respectively. Subgroups were analyzed and are depicted in table. Conclusions: Using a large clinical trials database in mRCC, we explored the predictive value of eTS in mRCC. Our analyses showed that the conventional 30% tumor shrinkage threshold is too high and that a cut-off at approximately 10% early TS predicts PFS and OS in mRCC. This finding is confirmed by a recent report on observer variability of eTS in mRCC. eTS should be further explored as a novel endpoint for clinical studies in mRCC. eTS as predictor in mRCC. PFS sensitivity/specifity OS sensitivity/specifity all 7% 0.611/0.674 8% 0.603/0.632 1st line 11% 0.632/0.684 8% 0.596/0.621 2nd line 4% 0.530/0.724 5% 0.673/0.704 axitinib, sorafenib, sunitinib 10% 0.647/0.598 10% 0.653/0.659 temsirolimus 11% 0.652/0.631 12% 0.616/0.621 IFN 1% 0.728/0.621 1% 0.712/0.508