Cetuximab Improves Survival in Certain Patients with Colorectal Cancer

Investigators have found that patients with early tumor shrinkage and colon cancer expressing wild-type KRAS genes benefit from addition of cetuximab to standard therapy.

Investigators have found that patients with early tumor shrinkage and colon cancer expressing wild-type KRAS genes benefit from addition of cetuximab to standard therapy.

In 2009, a trial of Bristol-Myers Squibb's Erbitux (cetuximab) in patients with colorectal cancer reduced overall survival when added to standard therapy with capecitabine, oxaliplatin, and Genentech's Avastin (bevacizumab). Patients receiving cetuximab with standard therapy had shorter survival than patients who received standard therapy (9.4 months versus 10.7 months; P = .01). However, in a post-hoc analysis, survival was not significantly reduced in patients with wild-type KRAS genes (10.6 months for patients receiving standard therapy versus 10.5 months for patients receiving standard therapy plus cetuximab; P = .30).

The 2009 trial discourages future research with cetuximab in patients whose colorectal cancers express non—wild-type KRAS gene, but the subgroup finding led investigators to test combination therapy with cetuximab in patients with a confirmed wild-type KRAS gene and another positive prognostic factor—early tumor shrinkage.

Results of a 2013 analysis of 2 trials indicate that patients with metastatic colorectal cancer with a wild-type KRAS gene and early tumor shrinkage improved median survival by 6.8 months (14.1 months versus 7.3 months; P <.001). Cetuximab demonstrated a median 10.3-month advantage in overall survival (15.7 months versus 26.0 months; P = .006).

Use of cetuximab may offer significant benefits to some patients, but combination therapy with cetuximab requires judicious use. The 2009 study found that use of cetuximab in combination with a standard regimen for colorectal cancer shortened progression-free survival and overall survival in patients with a mutated KRAS gene.

The use of cetuximab in a carefully selected population of patients who can derive a benefit demonstrates the emerging importance of individualized treatment for cancer. Many new specialty medications require genetic testing of tumors before initiation of treatment. The availability of these new therapies highlights the growing importance of individualized therapy. As evidenced by the trials with cetuximab, treatments that may worsen survival in some patients with colon cancer may actually improve survival in others.