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How Mutational Burden Affects Survival in Metastatic Colorectal Cancer

By: Lauren Harrison, MS
Posted: Tuesday, April 23, 2019

In patients with metastatic colorectal cancer treated with first-line therapeutics, a low mutational burden along with BRAF and RAS mutations appear to be negative prognostic factors. Federico Innocenti, MD, PhD, of the University of North Carolina at Chapel Hill, and colleagues published the results of the CALGB/SWOG 80405 randomized phase III trial in the Journal of Clinical Oncology.

“Molecular DNA analysis of tumor alterations in patients with [metastatic colorectal cancer] can provide new tools to predict patient outcome and improve therapeutic decision making,” suggested the authors.

Primary tumors from 843 patients receiving bevacizumab (37%), cetuximab (38%), or a combination of both (25%) were used to find genetic markers of overall survival. Through a series of polymerase chain reaction, genotyping, and next-generation sequencing, researchers found that patients with a high tumor mutational burden had better overall survival than patients with a low mutational burden (hazard ratio = 0.73). The median mutational burden was 52 mutations/Mb for patients with microsatellite instability–high tumors, whereas those with microsatellite-stable tumors had a median of 6 mutations/Mb.

In addition, for those with microsatellite instability–high tumors, patients treated with bevacizumab compared with cetuximab had better overall survival (hazard ratio = 0.13). Patients with BRAF- and RAS-mutant tumors had shorter overall survival than patients with wild-type tumors (hazard ratio = 2.01 and 1.52, respectively). Those with wild-type NRAS, KRAS, and BRAF tumors had a median overall survival of 35.9 months, compared with 22.2 months if any of these three genes was mutated.

Disclosure: The study authors’ disclosure information may be found at ascopubs.org.



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