Real-world treatment patterns and outcomes based on RAS/BRAF status in metastatic colorectal cancer-Analysis of the Prospective Dutch Colorectal Cancer cohort

The treatment landscape for metastatic colorectal cancer (mCRC) has evolved into a continuum of care with an essential role for biomarkers and molecular subgroups. Treatment guidelines are primarily based on trial results; however, populations and outcomes differ from clinical practice. To support the interpretation of trial results and to assist in tailored patient counseling, we evaluated real-world treatment patterns and outcomes according to RAS/BRAF status. We included all patients diagnosed with BRAFV600E-mutated mCRC in 2015-2020, participating in the Prospective Dutch Colorectal Cancer cohort study, plus a 1:2 random selection of patients with RAS-mutated and double wild-type mCRC. We evaluated differences in administered lines of treatment (LOTs), local treatment, attrition rates, treatment duration, progression-free survival (PFS) and overall survival (OS). 178 BRAFV600E-mutated, 221 RAS-mutated, and 174 double wild-type patients were included. Of BRAFV600E-mutated patients, 26% received ≥3 LOTs, compared to 42% and 47% of the RAS-mutated and double wild-type patients, respectively (p = .002). Local treatment was performed in 25% of BRAFV600E-mutated, 43% of RAS-mutated, and 49% of double wild-type patients (p < .001). Median OS from diagnosis was 15.4, 24.1, and 32.6 months, respectively (p < .001) and loss of prognostic value of RAS/BRAF was observed from the 3rd LOT onwards (p = .17 and p = .54). This paper provides a comprehensive overview of the treatment landscape of mCRC per RAS/BRAF status in daily clinical practice. The observed substantial treatment heterogeneity within and between molecular subgroups underlines the importance of collecting real-world data to address post-trial knowledge gaps and to optimize individualized counseling for all mCRC patients.