Incorporation of PBRM1, BAP1, TP53 mutation status into the Memorial Sloan Kettering Cancer Center (MSKCC) risk model: A genomically annotated tool to improve stratification of patients (pts) with advanced renal cell carcinoma (RCC).

639Background: The MSKCC risk model, an established prognostic tool for metastatic RCC, integrates clinical + laboratory data, but is ignorant to tumor genomics. Mutations in BAP1, PBRM1, TP53, cumulatively found in over 50% of pts, have prognostic value in RCC. We sought to study the use of integrating mutation status into the MSKCC model using two large clinical trial datasets. Methods: Pts had received first line sunitinib or pazopanib on the phase III COMPARZ (training set, n = 357) or the phase II RECORD3 trial (validation set, n = 130). Genes were evaluated by next generation sequencing using archival tissue. Association of mutation status and overall survival (OS) was tested by multivariate Cox regression analysis (MVA) in the training set. An annotated model was constructed combining the original clinical variables and mutation status for the 3 genes. We compared risk group assignment and concordance index (c-index) for the original vs. new model in training and validation set. Results: Mutation s...