NGS Identifies Survival, Treatment Outcomes for Patients With CRC Genetic Mutations

Genetic alternations in colorectal cancer are linked to different survival and treatment outcomes, according to a study that used next-generation sequencing of tumor DNA. The study was published in Journal of Clinical Oncology.

Researchers determined tumor mutational burden (TMB) using next-generation sequencing, gene mutations using polymerase chain reaction, and microsatellite status with genotyping.

"This is an example of precision oncology, where using genetics, we are able to stratify tumor types that we once believed were homogeneous, and to identify new patient subgroups that might benefit from tailored therapies," University of North Carolina Lineberger's Federico Innocenti, MD, PhD, associate professor in the Eshelman School of Pharmacy Division of Pharmacotherapy and Experimental Therapeutics, explained in a statement.

Innocenti and colleagues analyzed mutations in tumors of 843 patients with first-line metastatic colorectal cancer in the CALGB/SWOG 80405 randomized phase 3 trial. The trial had found no statistically significant different in overall survival between patients treated with chemotherapy plus either bevacizumab or cetuximab. The researchers also examined associations between genetic mutations and data on patient responses to treatment and survival.

Patients with high TMB had longer overall survival than patients with low TMB, and patients with patients with microsatellite instability, or a lot of genetic repeats in their tumor DNA, had longer survival if they were treated with bevacizumab compared with cetuximab.

Patients with BRAF mutant tumors or extended RAS mutant tumors had shorter overall survival than patients with wild-type tumors. According to Innocenti, the study confirmed that mutation was a “strong negative prognostic factor.” Median survival for patients with BRAF mutation was 13.5 months compared with 30.6 months in patients without mutations.

"It is crucial to define which patients could be responsive to immunotherapy in this setting, and this study shows the first promising evidence to do so," Innocenti said.

Reference

Innocenti F, Ou F-S, Qu X, et al. Mutational analysis of patients with colorectal cancer in CALGB/SWOG 80405 identifies new roles of microsatellite instability and tumor mutational burden for patient outcome [published online March 13, 2019]. J Clin Oncol. doi: 10.1200/JCO.18.01798.