Association of hypomagnesemia with inferior survival in a phase III, randomized study of cetuximab plus best supportive care versus best supportive care alone: NCIC CTG/AGITG CO.17

M. M. Vickers, C. S. Karapetis, D. Tu, C. J. O'Callaghan, T. J. Price, N. C. Tebbutt, G. Van Hazel, J. D. Shapiro, N. Pavlakis, P. Gibbs, J. Blondal, U. Lee, J. M. Meharchand, R. L. Burkes, S. H. Rubin, J. Simes, J. R. Zalcberg, M. J. Moore, L. Zhu, D. J. Jonker

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Background: Cetuximab-induced hypomagnesemia has been associated with improved clinical outcomes in advanced colorectal cancer (CRC). We explored this relationship from a randomized clinical trial of cetuximab plus best supportive care (BSC) versus BSC alone in patients with pretreated advanced CRC. Patients and methods: Day 28 hypomagnesemia grade (0 versus ≥1) and percent reduction (<20% versus ≥20%) of Mg from baseline was correlated with outcome. Results: The median percentage Mg reduction at day 28 was 10% (-42.4% to 63.0%) for cetuximab (N = 260) versus 0% (-21.1% to 25%) for BSC (N = 251) [P < 0.0001]. Grade ≥1 hypomagnesemia and ≥20% reduction from baseline at day 28 were associated with worse overall survival (OS) [hazard ratio, HR 1.61 (95% CI 1.12-2.33), P = 0.01 and 2.08 (95% CI 1.32-3.29), P = 0.002, respectively] in multivariate analysis including grade of rash (0-1 versus 2+). Dyspnea (grade ≥3) was more common in patients with ≥20% versus < 20% Mg reduction (68% versus 45%; P = 0.02) and grade 3/4 anorexia were higher in patients with grade ≥1 hypomagnesemia (81% versus 63%; P = 0.02). Conclusions: In contrast to prior reports, cetuximab-induced hypomagnesemia was associated with poor OS, even after adjustment for grade of rash.

Original languageEnglish
Pages (from-to)953-960
Number of pages8
JournalAnnals of Oncology
Issue number4
Publication statusPublished - Apr 2013
Externally publishedYes


  • Cetuximab
  • Colorectal cancer
  • Epidermal growth factor receptor
  • Hypomagnesemia
  • KRAS

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