Prognostic factors for patients with advanced renal cell carcinoma (aRCC) in the era of first-line (1L) treatment with immune checkpoint inhibitors (ICIs).

Abstract

4544 Background: The most commonly used prognostic models in aRCC, the Memorial Sloan-Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores, were developed when cytokines and VEGF targeted monotherapies were standard of care, respectively. aRCC 1L treatment now includes combination therapy with 2 ICIs or ICI+VEGF receptor inhibitor. Re-evaluation of the MSKCC and IMDC prognostic models in the era of ICI therapy and identification of additional prognostic factors are overdue. Methods: Data from 1052 patients with aRCC treated on the CheckMate-214 (CM214) clinical trial with 1L nivolumab/ipilimumab (NIVO/IPI) or sunitinib (SUN) were analyzed retrospectively at median follow-up 5 yrs. For each treatment group, multivariable Cox model hazard ratios (HR) were compared to the published MSKCC and IMDC model HRs. Discrimination (c index) was assessed based upon the continuous scores obtained as the weighted combination of regression parameters from the published MSKCC & IMDC models. Results: KPS < 80% remained highly prognostic in both treatment groups (HRs > 2.5). With the exception of high calcium, the other factors of time from dx to treatment < 1 yr, hemoglobin < lower limit of normal (LLN), neutrophils > upper limit of normal (ULN), platelets > ULN and LDH > 1.5xULN consistently retained prognostic value for SUN (HRs ≥ published model HRs) but had diminished prognostic value for NIVO/IPI (each HR < published model HR). High calcium had diminished prognostic value for SUN and retained prognostic value for NIVO/IPI. The c-indices for discrimination were 0.61 and 0.64 for the MSKCC model in the NIVO/IPI and SUN treatment groups, respectively, and were 0.63 and 0.67 for the IMDC model in the NIVO/IPI and SUN treatment groups compared to reported IMDC c-index of 0.73 (Heng 2009). (Table) Conclusions: The prognostic ability of the MSKCC and IMDC risk models is reduced with combination ICI treatment. Evaluation of additional prognostic factors and development of new risk scores are needed and this work is ongoing. [Table: see text]