Sistema de Salut de Catalunya
Institut Català de la Salut
[Hernando-Calvo A] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Kurzrock R] Worldwide Innovative Network (WIN) Association - WIN Consortium, Chevilly-Larue, France. Medical College of Wisconsin, Milwaukee, WI, USA. [Saoudi Gonzalez N] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. IFOM ETS – The AIRC Institute of Molecular Oncology, Milan, Italy. [Magidi S, Bresson C, Wunder F] Worldwide Innovative Network (WIN) Association - WIN Consortium, Chevilly-Larue, France. [Martin Casado A] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
2025-08-07T07:12:01Z
2025-08-07T07:12:01Z
2025-06-17
Cancer; Colorectal carcinoma; Precision oncology
Cáncer; Carcinoma colorrectal; Oncología de precisión
Càncer; Carcinoma colorectal; Oncologia de precisió
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 BRAF, MET, APC, TP53 and NRAS 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 BRAF V600E mutation), and regorafenib (may have WNT inhibitor activity relevant to APC mutation; VEGFR activity relevant since TP53 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.
The Molecular Tumor Board is fully supported by the Worldwide Innovative Network (WIN) Association - WIN Consortium.
Article
Published version
English
Còlon - Càncer - Aspectes genètics; Recte - Càncer - Aspectes genètics; Recte - Càncer - Tractament; Còlon - Càncer - Tractament; Metàstasi; Quimioteràpia combinada; ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols; DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Metastasis; DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms; Other subheadings::Other subheadings::Other subheadings::/drug therapy; DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms; Other subheadings::Other subheadings::Other subheadings::/genetics; TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada; ENFERMEDADES::neoplasias::procesos neoplásicos::metástasis neoplásica; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales; Otros calificadores::Otros calificadores::Otros calificadores::/genética
Impact Journals
Oncotarget;16
https://doi.org/10.18632/oncotarget.28744
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
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