Validation of imaging biomarker in a multicentric study to predict PFS in mRCC treated with TKI.

Abstract

526 Background: Tyrosine kinase inhibitors including sunitinib are the most effective treatments of metastatic renal cell carcinoma (mRCC). A multi-centric study of 539 patients (different tumors treated anti-angiogenic treatments) evaluating dynamic contrast-enhanced ultrasound (DCE-US), showed that a decrease of AUC (Area under the curve) correlated to the blood volume at one month is predictive of response. Our first objective was to validate the correlation between this parameter and the PFS in a sub-group of mRCC treated with Sunitinib The second objective was to study the variability of AUC. Methods: Each Patient had CT-scan every 2 months in order to evaluate the Response assessment using the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).DCE-US were performed at baseline and at D30. At each examination, we quantified 7 DCE-US parameters after bolus injection of contrast agent and mathematical modelization of raw linear data recorded during 3 minutes. We also estimated the variation between baseline and D30. The main endpoint was progression free survival assessed according to RECIST. We first selected the best parameters. We studied the trend between the parameter value and freedom from progression. After, the best cut-points were searched through a grid search. The best single cut-point was that with the lowest P-value for progression free survival. We performed this analysis in the sub-group of patients with mRCC treated with sunitinib. Morever, we studied the variability of AUC in 30 other patients treated with TKI . We performed in this group 2 DCE-US the same day before and after lunch. Results: A total of 81 mRCC patients treated with sunitinib were selected. All had DCE-US at baseline and one month. The median of follow-up was 18 months. For DCE-US, the decrease of 90 % of AUC at D 30 was correlated to the PFS (p =0.03). The difference of PFS between the groups defined by this cut-point was 4 months (bad responders) and 14 months (good responders). The results of variability are on-going. Conclusions: The decrease of more than 90% of AUC with DCE-US at one month is a potential predictive biomarker of response in mRCC patients treated with sunitinib. The results of variability of this parameter will be also presented. Clinical trial information: no. 912346.