Chemotherapy, Bevacizumab, and Cetuximab in Metastatic Colorectal Cancer

Oncogenic mutations as predictive factors in colorectal cancer

“…In addition to their predictive value, BRAF mutations seem to be a poor prognostic factor, independently of the administration of an anti-EGFR therapy, as it was observed in the CAIRO-2 study, a phase III randomized trial in which capecitabine, oxaliplatin and bevacizumab was compared with the same combination plus cetuximab in first-line treatment (Tol et al, 2009a;Tol et al, 2009b). In this study, progression-free and overall survival of patients with a BRAF mutation were dramatically reduced compared with that of patients with a KRAS mutation, and of course to that of KRAS/ BRAF wild-type patients, in both arms with and without cetuximab (Tol et al, 2009b).…”

Optimization of drug combinations using Feedback System Control

“…In a clinical setting, drug combinations are still mainly selected on the basis of empirical approaches, which are largely guided by clinical experience with individually administered drugs 31,32 . However, many optimization methods have been and are being evaluated preclinically 29,33,34 .…”

Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy?

“…31 In the CAIRO-2 (CApecitabine, IRinotecan, and Oxaliplatin trial) study, the addition of cetuximab to capecitabine, oxaliplatin, and bevacizumab as first-line treatment in patients with metastatic CRC had no effect on progression-free interval among those with tumors carrying WT KRAS (10.6 months in the chemotherapy-bevacizumab arm vs 10.5 months in the combined cetuximab arm). 32 In the large COIN trial the addition of cetuximab to Oxaliplatinbased CT did not improve OS or PFS with increased nonhematological toxicity in KRAS wt patients, even if the very advanced disease in the COIN population may be the reason for the negative results.. 33 …”