The very favorable metastatic renal cell carcinoma (mRCC) risk group: Data from the International Metastatic RCC Database Consortium (IMDC).
Andrew Schmidt, Wanling Xie, Chun Loo Gan, Connor Wells, Shaan Dudani, Frede Donskov, Camillo Porta, Cristina Suárez, Bernadett Szabados, Lori Wood, José Manuel Ruiz Morales, Ben Tran, Georg A. Bjarnason, Takeshi Yuasa, Benoit Beuselinck, Aaron R. Hansen, Neeraj Agarwal, Ziad Bakouny, Daniel Yick Chin Heng, Toni K. Choueiri
Abstract
339 Background: The IMDC criteria have been used as a prognostic tool for patients with mRCC receiving single agent VEGF-targeted drugs, and more recently combination immuno-oncology (IO) +/- VEGF-targeted agents, which improve outcomes over VEGF TKI monotherapy. We sought to identify a subset of patients with very favorable outcomes, for which less intensive therapy might be considered. Methods: Utilizing the IMDC dataset, 1638 patients with IMDC favorable risk disease received first-line systemic therapy. Patients were randomly selected in a 2:1 ratio to the training and testing sets, stratified by year of systemic therapy initiation. Multivariable Cox regression estimated prognostic factors for overall survival (OS). Results: Median age was 63 (range 21-95) years and 98% had received prior nephrectomy. First-line systemic therapy consisted of targeted therapy (91%), IO-combination regimens (8%), or other (1%). From the training data, three variables (primary diagnosis to systemic therapy <3 vs ≥3yr; Karnofsky Performance Status 80 vs >80; presence of brain, liver, or bone metastasis) significantly predicted for OS in the multivariable model (hazard ratio 1.4~1.5, p-values<0.05). The model had similar performance in the test dataset (C-index=0.64). Using the 3 included risk factors, patients were classified to very favorable risk (0 risk factors, 29% of patients) or favorable risk disease (≥1 risk factors, 71% of patients). Clinical outcomes for the two risk groups are presented in the table below. Conclusions: We identified a very favorable risk group in the IMDC criteria in RCC patients treated with first-line therapy. External validation including populations receiving IO containing therapies is ongoing. [Table: see text]