Prolonged response to combined BRAF and MEK inhibition in BRAF mutant colorectal cancer, a case report.

Background: BRAF V600E-mutant metastatic colorectal cancer (BRAF mCRC) is often associated with limited durable responses. After the publication of the randomized phase III BEACON trial investigating chemo-free regimens including BRAF inhibitors, anti-EGFR drugs, and MEK inhibitors (MEKis) in pre-treated BRAF mCRC patients, no MEKis have entered into clinical practice so far. Moreover, the recent phase III BREAKWATER trial investigating the first-line treatment of BRAF mCRC patients did not include MEKis at all. We present a compelling clinical case of a patient with BRAF mCRC who has experienced an extraordinary response to his MEKi-based treatment. Case presentation: In 2019 a 60 years old male patient was diagnosed with BRAF mCRC (peritoneal metastases). The patient was asymptomatic, with PS 0. He was started on first-line treatment with FOLFOXIRI plus bevacizumab and after 8 cycles underwent curative surgery. One year later, due to peritoneal relapse, second-line treatment with the BRAF inhibitor vermurafenib combined to the MEKi cobimetinib was started within a phase II clinical trial. The patient has maintained stable disease with manageable side effects over nearly four years. He is still alive and in good clinical conditions. Conclusion: The prolonged progression-free survival seen in the present clinical case represents, to our knowledge, the longest documented response to a MEKi-based regimen in this setting, supporting the hypothesis that MEKis deserve reconsideration in mCRC treatment. This case highlights the value of personalized genomic profiling and practical clinical decision-making, offering insights into treatment sequencing, resistance mechanisms, and future targeted therapy strategies in BRAF mCRC.