Efficacy of Second-line Targeted Therapy for Renal Cell Carcinoma According to Change from Baseline in International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Category

Background: We hypothesized that changes in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic category at start of second-line therapy (2L) for metastatic renal cell carcinoma (mRCC) might predict response. Objective: To assess outcomes of 2L according to type of therapy and change in IMDC prognostic category. Design, setting, and participants: We performed a retrospective review of the IMDC database for mRCC patients who received first-line (1L) VEGF inhibitors (VEGFi) and then 2L with VEGFi or mTOR inhibitors (mTORi). IMDC prognostic categories were defined before each line of therapy (favorable, F; intermediate, I; poor, P). Data were analyzed for 1516 patients, of whom 89% had clear cell histology. Intervention: All included patients received targeted therapy for mRCC. Outcome measurements and statistical analysis: Overall survival (OS), time to treatment failure, and response to 2L were analyzed using Cox or logistic regression. Results and limitations: At start of 2L, 60% of patients remained in the same prognostic category; 9.0% improved (3% I -> F; 6% P -> I); 31% deteriorated (15% F -> I or P; 16% I -> P). Patients with the same or better IMDC prognostic category had a longer time to treatment failure if they remained on VEGFi compared to those who switched to mTORi (adjusted hazard ratio [AHR] ranging from 0.33 to 0.78, adjusted p < 0.05). Patients who deteriorated from F to I appeared more likely to benefit from switching to mTORi (median OS 16.5 mo, 95% confidence interval [CI] 12.0-19.0 for VEGFi; 20.2 mo, 95% CI 14.3-26.1 for mTORi; AHR 1.53, 95% CI 1.04-2.24; adjusted p = 0.03). Conclusions: Changes in IMDC prognostic category predict the subsequent clinical course for patients with mRCC and provide a rational basis for selection of subsequent therapy. Patient summary: The pattern of treatment failure might help to predict what the next treatment should be for patients with metastatic renal cell carcinoma. (C) 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.