Several large randomized clinical trials have shown no benefit for either Erbitux® (cetuximab) or Vectibix™ (panitumumab) for patients whose tumors have mutations in the KRAS gene.
Both Erbitux and Vectibix block the activity of the epidermal growth factor receptors (EGFR) on cancer cells. Epidermal growth factor is a protein that promotes the growth of cells, including cancer cells.
Studies that compared wild-type and mutated KRAS and response to EGFR targeted therapies
The CRYSTAL study randomized patients who had not been previously treated for metastatic colorectal cancer to either FOLFIRI chemotherapy alone or FOLFIRI plus Erbitux.
- 35 percent of patients had KRAS mutations in their tumors.
- Patients with wild-type (normal) KRAS had significantly better response to treatment and progression-free survival when they got Erbitux in addition to chemotherapy.
- When tumors had mutated KRAS there was no difference in either response rate or progression-free survival when Erbitux was added to FOLFIRI.
The OPUS study compared FOLFOX alone to FOLFOX plus Erbitux, again for the initial treatment of metastatic colorectal cancer.
- When the KRAS mutation groups were considered separately there there was an improvement in response rate for the wild-type group with Erbitux — an increase from 37 percent to 61 percent. Progression-free survival was almost 50 percent better, as well.
- When there was a mutation in tumor KRAS, response rate appeared to fall somewhat when Erbitux was added to FOLFOX, although this was not significant. Progression-free survival was actually worse in the FOLFOX plus Erbitux group when compared to the group that received FOLFOX alone.
Finally, Vectibix, alone as monotherapy, was compared to best supportive care for patients with metastatic colorectal cancer whose cancer had already gotten worse on all the standard treatments.
- 43 percent of patients in the study had a mutation in KRAS in their tumors.
- 17 percent of patients with wild-type KRAS had responses to Vectibix. They had longer progression-free survival and lived longer than those who received supportive care alone.
- No patients with mutant KRAS had responses to Vectibix, and there was no improvement in progression-free survival.
- Patients with wild-type KRAS had improved quality of life when treated with Vectibix, but those with mutated KRAS had their quality of life get worse during treatment.
Where Can You Go for More Information
More information about the CRYSTAL and OPUS clinical trials from presentations at the 2008 American Society of Clinical Oncology meeting is available from C3 Research and Treatment News with links to the studies.
Information about the Vectibix trial from a presentation at the 2008 GI Symposium is available from C3 Research and Treatment News.
A video presentation by Dr. Rafael Amado from the 2008 GI Symposium discusses the wild-type and KRAS mutations in the Vectibix vs best supportive care randomized clinical trial. This is highly technical material but includes both Dr. Amado’s talk and his slides.
The June 10, 2008 NCI Cancer Bulletin reports on KRAS research with links to additional information.