Braun MS et al. – Topoisomerase-1 (Topo1) immunohistochemistry identified advanced colorectal cancer subpopulations that did/did not benefit from irinotecan and possibly from oxaliplatin; this data may contribute to individualization of treatment Methods
Study of candidate predictive biomarkers for irinotecan and oxaliplatin in advanced colorectal cancer
Review of 1,628 pts from the randomized trial Fluorouracil, Oxaliplatin, CPT-11: Use and Sequencing (FOCUS), comparing fluorouracil alone vs fluorouracil/irinotecan and vs fluorouracil/oxaliplatin
In biomarker screen in >750 pts for interaction with benefit from irinotecan or oxaliplatin, only 2 markers (Topo1; MLH1/MSH2) met criteria for further analysis
Primary end points: progression-free survival (PFS); overall survival (OS)
PFS: with addition of either irinotecan or oxaliplatin, no improvement in low Topo1 pts vs benefit in moderate/high Topo1 pts
OS: major benefit with first-line combination chemotherapy (median benefit, 5.3 mo) for high Topo1 pts vs no benefit (1.09 mo) for moderate or low Topo1 pts
MLH1/MSH2 had no significant interaction with treatment; low rate of loss (4.4%) limited study power for this biomarker
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