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- Title
BRAF V600E and RNF43 Co-mutations Predict Patient Outcomes with Targeted Therapies in Real-World Cases of Colorectal Cancer.
- Authors
Quintanilha, Julia C F; Graf, Ryon P; Oxnard, Geoffrey R
- Abstract
Anti-BRAF/EGFR therapy is approved for metastatic colorectal cancer (mCRC) with BRAF V600E mutations, although not all patients respond. Novel recent findings indicate the potential of RNF43 mutations to predict outcomes in patients with BRAF- mutated microsatellite stable (MSS) mCRC treated with anti-BRAF/EGFR therapy. This study aimed to independently and rapidly validate BRAF V600E/ RNF43 co-mutations as predictive biomarkers of benefit to anti-EGFR/BRAF therapy. Clinical data were derived from electronic health record data from ~280 US cancer clinics between January 2011 and March 2022 from the Flatiron Health-Foundation Medicine real-world clinico-genomic mCRC database. Real-world cases of BRAF V600E-mutated mCRC, with patients receiving anti-BRAF/EGFR therapy (n = 49), were included. Patients who were MSS, with RNF43 mutations, had favorable progression-free survival (hazard ratio [HR] 0.29; 95% CI [CI], 0.13-0.65) and overall survival (HR 0.32, 95% CI, 0.12-0.84) compared with wild type. No difference in outcomes was observed between patient groups with RNF43- mutant versus wild-type receiving standard-of-care chemotherapy. BRAF V600E/ RNF43 co - mutations predict mCRC anti-BRAF/EGFR outcomes in diverse clinical settings.
- Subjects
BIOMARKERS; GENETIC mutation; CONFIDENCE intervals; ANTINEOPLASTIC agents; ACQUISITION of data; RETROSPECTIVE studies; COLORECTAL cancer; TREATMENT effectiveness; TRANSFERASES; GENES; MEDICAL records; GENOMICS; PROGRESSION-free survival; LONGITUDINAL method; PHARMACODYNAMICS
- Publication
Oncologist, 2023, Vol 28, Issue 3, pe171
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1093/oncolo/oyac265