Loading
Pooling four large first-line trials, 3,063 patients, showed that broken DNA repair is rare in advanced bowel cancer and that the poor outlook it carries is really the poor outlook of the BRAF mutation that so often comes with it.
A pooled analysis of four phase 3 first-line studies in metastatic colorectal cancer assessed the prevalence and prognostic value of mismatch repair status and its relation to BRAF mutation, using Cox regression on individual patient data. Of 3,063 primary tumours analysed, 153 (5.0%) showed deficient mismatch repair and 250 (8.2%) a BRAF mutation. BRAF mutation was present in 53 of 153 (34.6%) deficient tumours against 197 of 2,910 (6.8%) proficient tumours. Both markers conferred an inferior prognosis: deficient mismatch repair gave hazard ratios of 1.33 for progression-free and 1.35 for overall survival, and BRAF mutation 1.34 and 1.91. Progression-free and overall survival were significantly worse for BRAF mutation within the proficient group, but BRAF status did not separate outcomes within the deficient group, nor did mismatch repair status within either BRAF group.
It fixes the metastatic prevalence figures every subsequent trial design has used, and it separates two biomarkers that travel together: BRAF, not mismatch repair deficiency, is what makes the prognosis bad.
Shares Radboudumc Centre for Oncology, Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR), MSI and mismatch-repair testing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2).
Shares BRAF V600E (and V600K), MSI and mismatch-repair testing, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Mismatch repair & microsatellite instability.
Shares BEACON CRC, BRAF V600E (and V600K), Encorafenib, BRAF.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Mismatch repair & microsatellite instability, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), BRAF.
Shares MSI and mismatch-repair testing, MSI-high (microsatellite instability by PCR or sequencing), Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares BEACON CRC, BRAF V600E (and V600K), Encorafenib, BRAF.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Mismatch repair & microsatellite instability, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), BRAF.
Shares KEYNOTE-177, Microsatellite-stable (MSS) / mismatch-repair proficient (pMMR), MSI and mismatch-repair testing, MSI-high (microsatellite instability by PCR or sequencing).