Clinical ReportsPredictive and prognostic value of magnesium serum level in FOLFIRI plus cetuximab or bevacizumab treated patients with stage IV colorectal cancer: results from the FIRE-3 (AIO KRK-0306) studySchulz, Christopha; Heinemann, Volkera; Heinrich, Kathrina; Haas, Michaela; Holch, Julian W.a; Fraccaroli, Alessiaa; Held, Swantjeb; von Einem, Jobst C.c; Modest, Dominik P.c; Fischer von Weikersthal, Ludwigd; Kullmann, Franke; Moehler, Markusf; Scheithauer, Wernerg; Jung, Andreash; Stintzing, SebastiancAuthor Information aDepartment of Medicine III, University Hospital, Ludwig Maximilian University (LMU), Munich bClinAssess GmbH, Leverkusen cDivision of Hematology, Oncology and Tumor Immunology (CCM), Department of Medicine, Charité - Universitaetsmedizin Berlin, Berlin dDepartment of Hematology and Oncology, Gesundheitszentrum St. Marien, Amberg eDepartment of Medicine I, Klinikum Weiden, Weiden fDepartment of Medicine II, University Hospital, Johannes Gutenberg University Clinic Mainz, Mainz, Germany gDepartment of Internal Medicine I and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria hInstitute of Pathology, University of Munich, Munich, Germany Received 10 April 2020 Revised form accepted 30 May 2020 Correspondence to Sebastian Stintzing, MD, Division of Hematology, Oncology, and Tumor Immunology (CCM), Department of Medicine, Charité Universitaetsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany, Tel: +49 30 450 513 002; fax: +49 30 450 513 952; e-mail: email@example.com Anti-Cancer Drugs: September 2020 - Volume 31 - Issue 8 - p 856-865 doi: 10.1097/CAD.0000000000000965 Buy Metrics Abstract Magnesium wasting is a frequent side effect of epidermal growth factor receptor (EGFR)-antibody treatment as magnesium-absorption mechanisms are dependent on EGFR signaling. EGFR-inhibition results in decreased renal reabsorption. There is evidence that hypomagnesemia during cetuximab treatment correlates with response. The prognostic role of hypomagnesemia during bevacizumab treatment has not been studied yet. Here, we evaluate the prognostic value of hypomagnesemia in patients with metastatic colorectal cancer treated with FOLFIRI plus cetuximab or bevacizumab as first-line therapy. A total of 391 of 752 patients of the firstline irinotecan study population had magnesium levels measured at baseline and for the first three cycles (6 weeks) of treatment. Of those, 240 had Rat Sarkoma wildtype tumors. Overall hypomagnesemia was more common in the cetuximab compared to the bevacizumab arm (80 vs. 43%, P < 0.005). During therapy, magnesium showed a time-dependent decrease to 80% of baseline in the cetuximab and to 89% in the bevacizumab arm. Whereas magnesium continued to decrease over time in the cetuximab-treated patients, it remained stable in the bevacizumab-treated. Overall response rate (ORR) was associated with higher magnesium at week 6 (20.9 vs. 79.1%, P = 0.041). Bevacizumab-treated patients with magnesium levels below the median value at week 6 had a significantly longer progression-free survival (PFS; 11.7 vs. 9.9 months, P = 0.034; hazard ratio 0.73) and a trend towards longer overall survival (OS) (29.6 vs. 23.2 months, P = 0.089; hazard ratio 0.77). Hypomagnesemia at predefined time points and magnesium nadir had no significant effect on ORR, OS and PFS in the cetuximab arm. Our data show different magnesium kinetics in patients with metastatic colorectal cancer treated with cetuximab or bevacizumab. For patients treated with cetuximab, hypomagnesemia did not have an impact on response and survival. Hypomagnesemia might have a prognostic value in bevacizumab treatment. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.