Real-world characteristics and outcomes of patients with BRAFV600E-mutant metastatic colorectal cancer in Australia: the COALA project

Abstract

Background

BRAF^V600E-mutated metastatic colorectal cancer (mCRC) is a biologically distinct and clinically aggressive subtype associated with poor outcomes. Real-world data on this population remains limited, particularly within the Australian health care setting.

Patients and methods

The COALA study is a national, prospective registry-based observational analysis of patients with mCRC across 21 Australian institutions. Data were extracted from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) and TRACC-Select registries and included demographics, molecular profiles, treatment patterns and overall survival (OS). Uptake and impact of encorafenib plus cetuximab (EC), since being available in Australia from May 2019, were examined.

Results

Of 2976 patients tested for BRAF, 374 (13%) harboured BRAF^V600E mutations, including 53 (24%) of the 217 ‘very-young’ subset (<40 years of age). Overall, compared with wild-type (BRAF-wt) tumours, BRAF^V600E-mutated tumours were more likely to occur in females (55% versus 39%), and right-sided primaries (60% versus 28%) occur with deficient mismatch repair (dMMR) (24% versus 3%), and/or peritoneal metastases (36% versus 20%). Only 42% of BRAF^V600E patients received second-line (2L) treatment. OS was significantly shorter in BRAF^V600E versus BRAF-wt patients [hazard ratio (HR) 1.75, 95% confidence interval 1.5-2; median 16.6 versus 32.3 months]. Among BRAF^V600E patients receiving 2L therapy, EC use versus chemotherapy was associated with a trend for improved OS (HR 0.70, median 8.6 versus 6.8 months).

Conclusions

The COALA study provides the first Australian real-world profile of BRAF^V600E-mutated mCRC. These findings underscore the importance of early and effective therapeutic strategies, and identify a novel, disproportionately affected very-young subgroup requiring targeted research and clinical focus.