Cetuximab is a monoclonal antibody that inhibits the epidermal growth factor receptor egfr which is present on the surface of some cancer cells. Severe infusion reactionsoccurred with the administration of 6 erbitux in approximately 3 % of patients, rarely with fatal outcome fire 3. A randomized phase iii study of folfiri plus cetuximab or bevacizumab as firstline treatment for wildtype wt kras exon 2 metastatic colorectal cancer mcrc patients s. Fire3 compared firstline 5fluorouracil, leucovorin, and irinotecan folfiri plus cetuximab with folfiri plus bevacizumab in patients with. Cetuximab is produced in mammalian murine myeloma cell culture. An epidermal growth factor receptor monoclonal antibody for the treatment of colorectal cancer siufun wong, pharmd western university college of pharmacy, pomona, california abstract background. To merge pdfs or just to add a page to a pdf you usually have to buy expensive software. Fire 3 was a prospective, multicenter, openlabel phase iii study nct00433927, the design of which has been described elsewhere. Planned accrual is 284 evaluable patients per treatment arm.
Oxaliplatin antagonizes cetuximab effects on the cancer stem cells in the cms4 the presence of fibroblasts. No significant difference in pfs on cetuximab retreatment according to prior antiegfr response, interval length between prior antiegfrbased therapy and cetuximab retreatment, or other demographic. The fda granted in 2012 approval to cetuximab for use in combination with folfiri irinotecan, 5fluorouracil, and leucovorin for treatment of patients with kras mutationnegative, egfrexpressing metastatic colorectal cancer. Optimising the use of cetuximab in the continuum of care.
The antiepidermal growth factor receptor egfr monoclonal antibody cetuximab in combination with chemotherapy is a standard of care in the firstline treatment of ras wildtype wt metastatic colorectal cancer mcrc and has demonstrated efficacy in later lines. In combination with platinumbased chemotherapy and fluorouracil for the initial treatment of patients with a certain type of head and neck cancer whose tumor has returned. The eu clinical trials register currently displays 36883 clinical trials with a eudract protocol, of which 6085 are clinical trials conducted with subjects less than 18 years old. Folfiri plus cetuximab versus folfiri plus bevacizumab as firstline treatment for patients with metastatic colorectal cancer fire3. Folfiri plus cetuximab versus folfiri plus bevacizumab for metastatic colorectal cancer fire 3. Folfiri plus cetuximab versus folfiri plus bevacizumab for. In addition, the fire 3 investigators sought to understand their results compared with the results of the calgbswog 80405 study. Cetuximab is a recombinant human mouse chimeric epidermal growth factor receptor egfr monoclonal antibody. Erbitux cetuximab injection for intravenous use, is a sterile, preservativefree, clear, colorless solution, which may contain a small amount of visible, white, amorphous cetuximab particulates in a singledose vial.
Page 1 of 18 erbituxtm rx only 1 2 cetuximab 3 for intravenous use only. Influence on efficacy in fire 3 a randomized phase iii study of folfiri plus cetuximab or bevacizumab as firstline treatment for wildtype wt kras exon 2. The fire3 trial is a multicenter randomized phase iii trial investigating 5fu, folinic acid and irinotecan folfiri plus cetuximab versus folfiri plus bevacizumab in first line treatment of metastatic colorectal cancer. Grade 3 or 4 immediately and permanently,discontinue erbitux. In the past 15 years, several egfr antagonists have been approved for the treatment of nsclc and metastatic crc mcrc. Cetuximab, a recombinant chimeric monoclonal antibody, has been successfully used in the treatment of the head and neck and colorectal cancers. The register also displays information on 18700 older paediatric trials in scope of article.
Trying to understand differing results of fire3 and 80405. Fire 3 compared firstline 5fluorouracil, leucovorin, and irinotecan folfiri plus cetuximab with folfiri plus bevacizumab in patients with kras exon 2 wildtype metastatic colorectal cancer. Material and methods patient population and treatment study design. Therapeutic value of egfr inhibition in crc and nsclc. The same study also reported an exploratory analysis of a subgroup of patients with tumours that were wildtype at other ras genes kras and nras exons 24. Our servers in the cloud will handle the pdf creation for you once you have combined your files. Fire3 compared firstline 5fluorouracil, leucovorin, and irinotecan folfiri plus cetuximab with folfiri plus bevacizumab in patients with kras exon 2 wildtype metastatic colorectal cancer. Erbitux cetuximab metastatic colorectal cancer and. Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after erbitux administration. An additional study fire 3 of phase iii, openlabel design recruited 592 patients with kras exon 2 wildtype mcrc who has not received previous treatment. Impact of subsequent therapies on outcome of the fire3. The role of cetuximab in converting initially unresectable.
Revisiting oral fluoropyrimidine with cetuximab in. Epidermal growth factor receptor egfr plays a key role in tumour evolution, proliferation and immune evasion, and is one of the most important targets for biological therapy, especially for nonsmallcell lung cancer nsclc and colorectal cancer crc. Merck data at esmo 2018 congress highlight multiple therapeutics with potential to transform cancer care. Patients were initially recruited without regard to kras tumour mutation status. Patients were initially recruited without regard to. Cetuximab is a chimeric mousehuman monoclonal igg1 antibody, which binds to egfr, thereby inhibiting the interaction of epidermal growth factors with receptors.
Bevacizumab and cetuximab for colorectal cancer drug and. That study varied in a number of ways from fire 3 eg, it was significantly larger and employed either folfox or folfiri, but it essentially asked the same cetuximab versusbevacizumab question. Closely monitor serum electrolytes, including serum magnesium, potassium. Fire 3 is the first study to compare cetuximab plus folfiri to bevacizumab plus folfiri in 1 st line treatment of mcrc th ras l bl l ti i ll t blthe ras evaluable population was in all respects comparable. Medical necessity criteria page 3 23 cetuximab may also be used as a singleagent with or without sequential chemoradiation, or in combination with. Although cetuximab is shown to provide survival benefits in patients with ras wildtype metastatic colorectal cancer, little is known about the optimal chemotherapy backbone for cetuximab except that oral fluoropyrimidine appeared to be inferior to infusional fluoropyrimidine and is not recommended in various international guidelines. Data from the raswt population of the randomized, phase 3 fire 3 trial showed that the percentage of patients who discontinued treatment owing to their eligibility for secondary resection of metastases was comparable between patients who were treated with cetuximab plus folfiri vs those receiving bevacizumab plus folfiri 11. Merck today announced that new data from a variety of highpriority clinical development programs will be presented at the esmo 2018 congress, october 1923, 2018, munich, germany. The impact of primary tumor side on outcomes of first. The fire3 trial of the arbeitsgemeinschaft internistische onkologie aio was designed to explore whether cetuximab or bevacizumab was a more effective partner for folfiri in the firstline treatment of metastatic colorectal cancer.