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Validated Risk Model Integrates Molecular Features in Advanced Renal Cancer

By: Sarah Campen, PharmD
Posted: Thursday, January 3, 2019

For patients with metastatic renal cell carcinoma, the Memorial Sloan Kettering Cancer Center (MSKCC) risk model is an established prognostic tool that includes clinical and laboratory data; however, it does not account for a patient’s mutational status, which can have an effect on prognosis. Martin H Voss, MD, of MSK, New York, and colleagues have now combined somatic mutational data with the MSKCC risk model to create “the first validated model to integrate molecular features with clinical and laboratory parameters in the metastatic setting.” The results of the retrospective cohort study were published in The Lancet Oncology.

The researchers used 2 independent clinical trial data sets of patients with metastatic renal cell carcinoma assigned to receive treatment with tyrosine kinase inhibitors, including the COMPARZ trial (n = 357) for the training cohort and RECORD-3 trial (n = 258) for the validation cohort. They discovered that the presence of any mutation in BAP1 or TP53, or both, and the absence of any mutation in PBRM1 were prognostic in terms of overall survival.

Mutations in one or more of these genes occurred in more than 50% of cases in this setting, and integrating this information altered the risk categorization for approximately half the patients across the two cohorts. The updated MSKCC risk model, which was confirmed to be superior in multiple analyses, “warrants further investigation in prospective trials,” concluded Dr. Voss and colleagues. “[It] could be applied for prognostication of individual patients in future clinical trials.”

Disclosure: Study authors’ disclosure information may be found at The Lancet Oncology.



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