Case Report WIN-MTB-2023001 WIN International Molecular Tumor Board A 62-year-old male with metastatic colorectal cancer with 5 prior lines of treatment.

Heavily pretreated metastatic colorectal cancer (mCRC) poses significant therapeutic challenges. Advances in molecular profiling enables personalized strategies. We present a 62-year-old male with mCRC harboring , , , and alterations, following FOLFOX and FOLFIRI, dabrafenib plus panitumumab, and a BRAF inhibitor clinical trial, each leading to initial responses followed by disease progression. WIN Consortium International Molecular Tumor Board (MTB), included experts from institutions across 13 countries. Enrollment in suitable clinical trials was explored but limited by availability. Personalized combinations suggested included amivantamab-vmjw (anti-MET/EGFR antibody) (one-third standard dose) (for MET amplification and due to prior response to anti-EGFR antibody), trametinib, 1 mg po daily (MEK inhibitor for mutation), and regorafenib (may have WNT inhibitor activity relevant to mutation; VEGFR activity relevant since alterations upregulate VEGF/VEGFR axis) starting at 40 mg po daily three weeks on, one week off. Another option was trametinib at 1 mg daily, cetuximab (EGFR antibody), 250 mg/m² IV every two-weeks, and cabozantinib (MET and VEGFR inhibitor), 40 mg po daily. FOLFOXFIRI combined with bevacizumab, or liver-directed therapies for hepatic metastases, or regorafenib with 5FU, or crizotinib (MET inhibitor) combined with regorafenib or dabrafenib, was also suggested. This case emphasizes the critical role of comprehensive molecular profiling and personalized therapeutic approaches in managing complex mCRC. The WIN International MTB aims to provide treatment and biomarker analysis discussion with the ultimate goal of optimizing treatment efficacy by targeting specific molecular alterations, though final treatment decisions remain at the discretion of the treating physician.