The FDA has approved Erbitux™ (cetuximab) in combination with FOLFIRI for first-line treatment of patients with metastatic colorectal cancer whose tumors have a wild-type (WT) KRAS gene. Erbitux was first approved in 2004 for patients whose cancer was not responding to available treatments.
FDA’s action was prompted by results from a look back at patient outcomes and KRAS status from three trials:
- CRYSTAL: phase 3, 1217 patients newly diagnosed with metastatic CRC, comparing FOLFIRI vs FOLFIRI + Erbitux
- OPUS: phase 2, 337 patients newly diagnosed with metastatic CRC, comparing FOLFOX vs FOLFOX + Erbitux
- CA225025: phase 3, 572 patients with metastatic CRC that stopped responding to available treatments, comparing Best Supportive Care (BSC) to BSC + Erbitux
In June 2008, data from CRYSTAL and OPUS showed that patients with mutated KRAS genes did not respond to treatment with Erbitux. As a result, the FDA modified the labels of Erbitux and Vectibix™ (panitumumab), a drug that is similar to Erbitux, to say that patients with mutated KRAS genes should not be treated with Erbitux or Vectibix.
Additional analyses of CRYSTAL showed that that patients with non-mutated (wild type, WT) KRAS who received both FOLFIRI and Erbitux as first-line treatment lived on average 23.5 months, compared to 19.5 months for patients who received FOLFIRI alone. Data from OPUS and CA225025 also showed that patients with non-mutated (wild-type) KRAS responded to treatment with Erbitux, and confirmed that patients with mutated KRAS did not respond.
As a result, FDA has approved use of FOLFIRI plus Erbitux for first-line treatment. FDA also noted that these analyses confirmed the existing side effect profile of Erbitux. The National Comprehensive Cancer Network (NCCN) treatment guidelines indicate that the following are all first-line treatment options:
- Avastin ™ (bevacizumab) plus FOLFOX or FOLFIRI
- Vectibix plus FOLFOX or FOLFIRI
- Erbitux plus FOLFIRI
- FOLFOXIRI (in limited cases)
These options should be covered by most insurance companies, which use NCCN guidelines as a basis for coverage decisions.
- FDA announcement of approval
- Erbitux label
- CRYSTAL data published in 2009 New England Journal of Medicine
- Call Fight CRC’s Answer Line at 1-877-427-2111
What this means for patients:
- If you are newly diagnosed with metastatic colorectal cancer and if your tumor has wild type (non-mutated) KRAS genes, you can talk with your doctor about options for first-line treatment, and how first-line treatment will evolve to successive lines of treatment.
- If you are newly diagnosed and your tumor has mutated KRAS genes, you should not be treated with Erbitux or Vectibix.
Disclosure: Fight CRC has accepted funding for projects and educational programs from Amgen, Imclone Systems, Bristol Myers Squibb, and Eli Lilly in the form of unrestricted educational grants. Fight CRC has ultimate authority over website content.