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

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. Day 28 hypomagnesemia grade (0 versus >= 1) and percent reduction (< 20% versus >= 20%) of Mg from baseline was correlated with outcome. 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). In contrast to prior reports, cetuximab-induced hypomagnesemia was associated with poor OS, even after adjustment for grade of rash.