Oncotarget

Precision Oncology:

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

Alberto Hernando-Calvo, Razelle Kurzrock, Nadia Saoudi Gonzalez, Shai Magidi _, Catherine Bresson, Fanny Wunder, Giulia Pretelli, Agatha Martin Casado and Wafik S. El-Deiry

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Oncotarget. 2025; 16:456-466. https://doi.org/10.18632/oncotarget.28744

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Abstract

Alberto Hernando-Calvo1,2,*, Razelle Kurzrock3,4,*, Nadia Saoudi Gonzalez1,2,5, Shai Magidi3, Catherine Bresson3, Fanny Wunder3, Giulia Pretelli1,2, Agatha Martin Casado2 and Wafik S. El-Deiry3,6,*

1 Vall d’Hebron University Hospital, Barcelona, Spain

2 Vall d’Hebron Institute of Oncology, Barcelona, Spain

3 Worldwide Innovative Network (WIN) Association - WIN Consortium, Chevilly-Larue 94550, France

4 Medical College of Wisconsin, Milwaukee, WI 53226, USA

5 IFOM ETS – The AIRC Institute of Molecular Oncology, Milan, Italy

6 Legorreta Cancer Center at Brown University, Providence, RI 02903, USA

* These authors contributed equally to this work

Correspondence to:

Shai Magidi, email: [email protected]

Keywords: cancer; precision oncology; molecular tumor board; colorectal carcinoma; cancer management

Received: March 11, 2025     Accepted: May 30, 2025     Published: June 17, 2025

Copyright: © 2025 Hernando-Calvo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

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.


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