Vemurafenib added to Cetuximab and irinotecan in Advanced Colorectal Cancer

In a recent publication in the JCO investigators from the Southwest oncology group report on trial results of SWOG S1406 trial of irinotecan and cetuximab with or without vemurafenib in BRAF mutated metastatic colorectal cancer

In this randomized trial, 106 patients with BRAF V600E mutated metastatic colorectal cancer, who had received either a single or two lines of therapy were randomized to a combination of irinotecan plus cetuximab with or without the addition of 960 mg twice daily oral vemurafenib. The primary endpoint was progression free survival.

Investigators reported a hazard ratio of 0.50, P=0.001 with the addition of vemurafenib. The response rate was 17% versus 4%, with a P-value of 0.05. Circulating tumor DNA variant allele low-frequency was seen in 87% versus 0% of patients, P < 0.001, with a low prevalence of acquired RAS alterations at progression. RNA profiling studies showed that previously determined subgroups for BRAF or molecular subtype did not predict treatment benefit.

The authors concluded that targeting both EGFR and BRAF coupled with irinotecan and BRAF V600E mutated colorectal cancer was efficacious.