Colon Cancer

Randomized Trial of Irinotecan and Cetuximab with or without Vemurafenib in BRAF Mutated Metastatic Colorectal Cancer (SWOG S1406)


The purpose of the study was to test the efficacy of the addition of vemurafenib to irinotecan and cetuximab, given the limited efficacy of monotherapy with vemurafenib and BRAF V600E mutated advanced colorectal cancer.

106 patients with BRAF V600E mutated metastatic colorectal cancer, previously treated with up to 2 regimens, were randomly assigned to receive irinotecan and cetuximab with or without vemurafenib. Vemurafenib was dosed at 960 mg twice daily.

The primary endpoint was progression free survival.  The addition of vemurafenib improved progression free survival, hazard ratio 0.50, P = 0.001.  The response rate was 17% versus 4%, P = 0.05.  The disease control rate was 65% versus 21%, P < 0.001.  Decline in circulating tumor DNA BRAF V600E variant allele frequency was seen in 87% versus 0%, P value < 0.001.  There was a low incidence of acquired RAS alterations at the time of progression.

The authors concluded “simultaneous inhibition of EGFR and BRAF combined with irinotecan is effective in BRAF V600E mutated colorectal cancer.”