Erbitux® (cetuximab) improves overall and progression-free survival while maintaining quality of life for many patients with colon cancer.
Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Advanced colorectal cancer refers to cancer that has spread from its site of origin, beyond the colon and nearby lymph nodes. Standard treatment for advanced colorectal cancer typically includes surgery (if possible), chemotherapy and NGS biomarker testing for cancer growth causing mutations that can be targeted with precision cancer medicines.
About Erbitux
The Food and Drug Administration (FDA) has approved Erbitux™ (cetuximab) for the treatment of metastatic colorectal cancer that expresses the epidermal growth factor receptor (EGFR), Erbitux™ was the first monoclonal antibody that has been approved for the treatment of colorectal cancer. It is targeted against the EGFR pathway, which is implicated in the initiation and/or continuation of the growth of cancerous cells. Erbitux™ binds to a specific site in the EGFR pathway, which blocks or reduces the growth-stimulatory effects of EGFR on cancer cells. EGFR is most commonly present on colon cancers involving the left side of the colon and rarely occurs elsewhere. Erbitux is also ineffective in cancers overexpressing the HER2 biomarker.
Erbitux® in First–Line Therapy of Metastatic Colorectal Cancer
The addition of Erbitux to the chemotherapy combination regimen known as FOLFOX4 improves response rates and shows promise as initial treatment for EGFR-positive, metastatic colorectal cancer.
This study included 43 patients with stage IV colorectal cancer positive for EGFR expression. Erbitux was given in combination with FOLFOX4, (Eloxatin, folinic acid and 5-fluorouacil) as The study found that disease control was achieved in 98% of the patients treated. The average duration of response was 330 days. The average duration of cancer free survival was 12.3 months and 52% of patients survived greater than 1 year. Side effects such as neurotoxicity, an acne-like rash, and diarrhea accounted for 9% of patients discontinuing therapy. Future trials comparing these two regimens are expected to determine the full benefit of the addition of Erbitux to FOLFOX4.5
Recurrent Colon Cancer
The clinical trial that prompted the FDA approval was conducted by researchers from England, who evaluated the addition of Erbitux™ to Camptosar (irinotecan) chemotherapy in patients with metastatic colorectal cancer that had stopped responding to previous therapy with irinotecan. The trial included 329 patients who had stopped responding to prior irinotecan either during treatment or within 30 days following treatment. Patients were then divided into two groups: those who were treated with Erbitux™ and irinotecan and those treated with Erbitux™ alone. The overall anti-cancer response rates were 23% for patients treated with Erbitux™ plus irinotecan, compared to 11% for those treated with Erbitux™. The average time to cancer progression was 4.1 months for patients treated with Erbitux™ plus irinotecan, compared to only 1.5 months for those treated with Erbitux™. The average duration of survival was 8.6 months for patients treated with Erbitux™ plus irinotecan, compared to 6.9 months for patients treated with Erbitux™ only. More patients experienced side effects in the group treated with Erbitux™ plus irinotecan, with diarrhea being the most common serious side effect.
To confirm whether the combination of Erbitux and the chemotherapy drug Camptosar® (irinotecan) is more effective than Camptosar alone, researchers conducted an international, Phase III clinical trial known as the Erbitux Plus Irinotecan in Colorectal Cancer (EPIC) study. The study enrolled more 1,298 patients with metastatic colorectal cancer that was resistant to Eloxatin® (oxaliplatin). Half the patients were treated with Camptosar alone and half were treated with a combination of Erbitux and Camptosar.
- Compared to patients treated with Camptosar alone, patients treated with Erbitux and Camptosar experienced a longer time to cancer progression.
- Overall survival did not differ between the study groups. The lack of a difference in overall survival may be due to the fact many patients initially treated with Camptosar alone began taking Erbitux after cancer progression.
- Side effects that were more common in patients taking both Erbitux and Camptosar included fatigue, diarrhea, and an acne-like rash.
Erbitux®/Avastin®/Camptosar®
The addition of the targeted agent Avastin® (bevacizumab) to treatment including the targeted agent Erbitux® (cetuximab), with or without the chemotherapy agent Camptosar® (irinotecan) also appears effective for patients with advanced colorectal cancer who do not respond to Camptosar alone.
Avastin is also a targeted agent that slows or prevents the growth or spread of some cancers by targeting the vascular endothelial growth factor receptor (VEGF), which is involved in supplying blood vessels to cancer cells. The blood vessels carry oxygen and nutrients to the cancer cells, allowing for their growth and spread.
Researchers from Memorial Sloan Kettering Cancer Center (MSKCC) recently conducted a clinical trial to evaluate Erbitux in the treatment of colorectal cancer patients with liver metastases. This trial included 83 patients with advanced colorectal cancer who did not respond to treatment with Camptosar alone. No patients had received prior therapy with Erbitux or Avastin. One group of patients was treated with Erbitux/Avastin/Camptosar, and the other group was treated with Erbitux and Avastin.
- Time to cancer progression was 7.3 months for patients treated with Erbitux/Avastin/Camptosar versus 4.9 months for those treated with Erbitux/Avastin.
- Anticancer responses were achieved in 37% of patients treated with Erbitux/Avastin/Camptosar versus 20% for those treated with Erbitux/Avastin.
- Overall survival was 14.5 months for patients treated with Erbitux/Avastin/Camptosar compared with 11.4 months for those treated with Erbitux/Avastin.
Connect With Others for Support and information
CancerConnect was the first social network created for people with colon cancer. Founded by oncologists to support cancer patients and their caregivers, over 40 million individuals have accessed CancerConnect programs since 1997. CancerConnect is used by leading cancer centers like Dana Farber, Roswell Park and The James at Ohio State to support their patients. Join the conversation, ask questions, share your experience, and learn how the best cancer centers are treating cancer from others. Share your experience, ask a question, or start a conversation by posting on CancerConnect.
References:
1. Jonker D, O’Callaghan C, Karapetis C, et al. Cetuximab for the treatment of colorectal cancer. New EnglandJournal of Medicine. 2007;357:2040-2048.
2. Sobrero AF, Fehrenbacher L, Rivera F et al. Randomized Phase III trial of cetuximab plus irinotecan vs. irinotecan alone for metastatic colorectal cancer (mCRC) in 1298 patients (pts) who have failed prior oxaliplatin-based yherapy: The EPIC Trial. Presented at the 2007 meeting of the American Association for Cancer Research, Los Angeles, CA, April 14-18, 2007. Abstract LB-2.
3. Saltz L, Lenz H-J, Kindler H, et al. Randomized Phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: The BOND-2 Study. Journal of Clinical Oncology. 2007;25:4557-4561.
4. ImClone Systems Inc. and Bristol-Myers Squibb Company. ErbituxM (Cetuximab) receives FDA approval to treat irinotecan refractory or intolerant metastatic colorectal cancer. Available at: http://www.erbitux.com/erbitux/pre/index.jsp?BV_UseBVCookie=Yes. Accessed February 2004.
5. Diaz-Rubio E, Tabernero J, Van Cutsem E, et al. Cetuximab in combination with oxaliplatin/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) in the first-line treatment of patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC): An international phase II study. Proceedings from the 2005 annual meeting of the American Society of Clinical Oncology. May 2005. Abstract #3535.
