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Treatment and Survival Outcome of BRAF-Mutated Metastatic Colorectal Cancer: A Retrospective Matched Case-Control Study
Authors:Hamzeh Kayhanian  Emily Goode  Francesco Sclafani  Joo Ern Ang  Marco Gerlinger  David Gonzalez de Castro  Scott Shepherd  Clare Peckitt  Sheela Rao  David Watkins  Ian Chau  David Cunningham  Naureen Starling
Affiliation:1. Gastrointestinal and Lymphoma Unit, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom;2. The Institute of Cancer Research, London, United Kingdom;3. Queen’s University Belfast, School of Medicine, Dentistry and Biomedical Sciences, Belfast, United Kingdom
Abstract:

Background

Somatic v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation, present in approximately 10% of metastatic colorectal cancer (mCRC) cases, is associated with poor prognosis. Patient outcome outside of clinical trials has only been reported in small series. We report real-world data on treatment and survival for BRAF-mutated (MT) patients at a single tertiary center, compared with a matched BRAF wild type (WT) control group.

Patients and Methods

All colorectal cancer patients tested for BRAF mutation, from October 2010 to November 2014 were identified. BRAF-MT mCRC cases were compared with an age and sex-matched BRAF-WT control group. Clinicopathological data were collected and survival calculated using the Kaplan–Meier method and comparisons made using Cox regression.

Results

Forty-three of 503 patients (8.5%) tested had BRAF-MT mCRC and were compared with 88 BRAF-WT controls. Median overall survival (mOS) was 18.2 months for BRAF-MT and 41.1 months for BRAF-WT mCRC patients (hazard ratio, 2.74; 95% confidence interval, 1.60-4.70; P < .001). Progression-free survival for BRAF-MT and WT patients, respectively, was: 8.1 months versus 9.2 months (P = .571) first-line, 5.5 months versus 8.3 months (P = .074) second-line, and 1.8 months versus 5.6 months (P = .074) third-line. Treatment using sequential fluoropyrimidine-based doublet chemotherapy was similar between both groups. Anti-epidermal growth factor receptor (EGFR) therapy was mainly given third-line with progressive disease in 90% (n = 9 of 10) of BRAF-MT patients at first restaging.

Conclusion

In this case-control study, the poor mOS of BRAF-MT mCRC was associated with reduced treatment benefit beyond first-line. Sequential doublet chemotherapy remains a reasonable option in appropriately selected patients. BRAF-MT patients did not benefit from anti-EGFR therapy in this study. Recruitment to clinical trials is recommended to improve outcomes in BRAF-MT mCRC.
Keywords:Anti-EGFR  Biomarker  Chemotherapy  Prognosis  Real-world
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