BRAF + MEK Inhibitors in mCRC
BRAF V600 mutations occur in up to 15% of patients with mCRC and predict poor prognosis. Unfortunately, BRAF inhibitor monotherapy has been largely ineffective in mCRC, but 2 presentations at ASCO 2014 examined the value of BRAF inhibition in combination with other targeted agents. In one study, 43 patients with BRAF V600 mutant stage IV mCRC were treated with the combination of dabrafenib plus the MEK inhibitor trametinib (Corcoran RB, et al. ASCO 2014. Abstract 3517). At a 6-month follow-up, 12% of the patients achieved a partial response or better, and 51% of the patients achieved stable disease. Neither PTEN loss nor microsatellite instability correlated with efficacy. Further biomarker delineation to select patients more precisely for this combination may help improve the results.