Association Between Regorafenib, Clinical Benefits in Patient Subgroups

the Cancer Therapy Advisor take:

Clinical benefits favoring regorafenib across patient subgroups (of patients with metastatic colorectal cancer) defined by mutations identified using BEAMing analysis were suggested by correlative data analysis, according to an article published online in the journal The Lancet Oncology.

Results showed KRAS mutations were identified in 349 out of 503 patients (69%), PIK3CA mutations were identified in 84 of 503 of patients (17%), and BRAF mutations in 17 of 502 of patients (3%), all of which were detected using BEAMing of plasma DNA.

No analysis was conducted on BRAF genotype because of the low frequency of mutations identified for this gene.

However, correlative analysis proposed clinical benefits favoring regorafenib in patients with the KRAS and PIK3CA mutations (progression-free survival [PFS] with regorafenib vs. placebo: HR, 0.52; 95% CI: 0.35, 0.76 for KRAS wild-type; HR, 0.51, 95% CI: 0.40, 0.65 for KRAS mutant [KRAS wild type vs. mutant, P=0.74]; HR, 0.50; 95% CI: 0.40, 0.63 for PIK3CA wild-type; HR, 0.54, 95% CI: 0.32, 0.89 for PIK3CA mutant [PIK3CA wild-type vs. mutant, P=0.85]) or circulating DNA concentration (PFS with regorafenib vs. placebo: HR, 0.53; 95% CI: 0.40, 0.71, for low circulating DNA concentrations; HR 0.52, 95% CI: 0.40, 0.70, for high circulating DNA concentrations; low vs. high circulating DNA, P=0.601).

Plasma protein concentrations and regorafenib were not statistically significantly associated with progression–free survival, with the exception of von Willebrand factor.

The only plasma protein with an association to overall survival was TIE-1, with high concentrations associated with longer overall survival.