Hypomagnesemia is Associated with Inferior Survival in Patients Receiving Cetuximab for Advanced Colorectal Cancer

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(ChemotherapyAdvisor) – Among patients with advanced colorectal cancer (CRC) who are treated with cetuximab, hypomagnesemia is associated with poor overall survival (OS), according to an analysis of data from the largest study of its kind to date, a phase 3 randomized study published in the Annals of Oncology.

“In contrast to prior reports, cetuximab-induced hypomagnesemia was associated with poor OS, even after adjustment for grade of rash,” reported lead author Michael M. Vickers, MD, of the Department of Oncology at Tom Baker Cancer Center, Calgary, Canada, and coauthors. “We have shown for the first time that hypomagnesemia at day 28 is associated with worse survival in patients treated with cetuximab, and that this biomarker has a greater predictive capacity than grade of rash.”

Among patients receiving cetuximab versus best supportive care only, median OS was 3.7 versus 8.0 months for grade ≥1 and 0 hypomagnesemia, respectively (HR 1.60, 95% CI, 1.10-2.31; P=0.01), the authors reported. A ≥20% reduction in Mg from baseline to day 28 was associated with worse OS, as well (HR 2.08, 95% CI, 1.32-3.29; P=0.002).

“Among patients with KRAS wild-type tumors, the results were similar,” the authors noted. “Higher grade of hypomagnesemia associated with worse OS (median 4.4 versus 9.9 months for grade ≥1 versus 0, respectively; adjusted HR 2.22 (95% CI, 1.10-4.51), P=0.03).” Among patients with KRAS wild-type tumor who received cetuximab treatment, 73 (81%) patients had grade 0 hypomagnesemia while 17 (19%) had grade ≥1 hypomagnesemia at day 28.

"Identifying the association of KRAS mutation status and EGFR monoclonal antibody therapy benefit “was a major step towards personalizing therapy in advanced CRC,” the authors reported.

Patients with KRAS wild-type tumor had a higher dose intensity and a <20% reduction in Mg from baseline; otherwise, dose intensity did not affect Mg percent reduction, they noted.

Hypomagnesemia at day 28 was associated with grade ≥3 anorexia (81% vs 63%; P=0.02; for patients with KRAS wild-type tumors, 88% vs 62%; P=0.05), the authors wrote. Dyspnea grade ≥3 was more common among patients experiencing ≥20% Mg reduction versus those experiencing <20% Mg reduction (68% vs 45%; P=0.02).

“Our study is the largest assessment of the cetuximab-induced hypomagnesemia on clinical outcomes in advanced CRC and is the first to show a deleterious effect of hypomagnesemia among patients with KRAS-mutated tumors,” the authors concluded. “Mg levels were analyzed locally at each center, making assessment of this possible biomarker available to clinicians.”

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