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The first randomised proof that a mutation can say a drug will not work: in a trial of cetuximab against supportive care alone, only patients whose tumours had a normal K-ras gene lived longer.
Tumour samples from 394 of 572 patients (68.9%) with colorectal cancer randomly assigned to cetuximab plus best supportive care or best supportive care alone were analysed for activating mutations in exon 2 of the K-ras gene. Of the tumours evaluated, 42.3% had at least one such mutation. The effectiveness of cetuximab was significantly associated with K-ras mutation status (interaction p = 0.01 for overall survival and p less than 0.001 for progression-free survival). In patients with wild-type tumours, cetuximab improved median overall survival from 4.8 to 9.5 months (hazard ratio 0.55) and progression-free survival from 1.9 to 3.7 months (hazard ratio 0.40). Among patients with mutated tumours there was no difference in overall survival (hazard ratio 0.98) or progression-free survival (hazard ratio 0.99). K-ras status was not associated with survival in the supportive-care group, so it is predictive rather than prognostic in this setting.
It created the negative predictive biomarker in solid tumour oncology and, with the panitumumab analysis of the same year, restricted EGFR antibodies to RAS wild-type disease worldwide.
Shares KRAS G12D (and other non-G12C KRAS mutations), Wild-type (WT), therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF), RAS / RAF / MEK / ERK (MAPK).
Shares Cetuximab, RAS / RAF / MEK / ERK (MAPK), EGFR, KRAS.
Shares Wild-type (WT), Cetuximab, RAS / RAF / MEK / ERK (MAPK), EGFR.
Shares Wild-type (WT), Cetuximab, EGFR, KRAS.
Shares Wild-type (WT), EGFR, KRAS, Colorectal cancer.
Shares Cetuximab, RAS / RAF / MEK / ERK (MAPK), EGFR, New England Journal of Medicine.
Shares Cetuximab, EGFR, KRAS, Colorectal cancer.
Shares KRAS G12D (and other non-G12C KRAS mutations), Wild-type (WT), RAS / RAF / MEK / ERK (MAPK), KRAS.