Bevacizumab and cetuximab for colorectal cancer drug and. Aug 10, 2015 purpose we investigated choice and efficacy of subsequent treatment, with special focus on secondline therapy, in the fire 3 trial folfiri plus cetuximab arm a or bevacizumab arm b for patients with kras wildtype metastatic colorectal cancer. Nct00433927 prospective, randomized trial investigated the efficacy of firstline treatment with folfiri plus either cetuximab or bevacizumab in 592 kras exon2 wildtype mcrc patients. The addition of cetuximab prolonged the median progressionfree survival time from 3. Folfiri plus cetuximab versus folfiri plus bevacizumab. Relation of cetuximabinduced skin toxicity and early tumor.
Docetaxel plus cetuximab biweekly is an active regimen for. Bevacizumab in the firstline treatment of metastatic colorectal cancer director of the study. Crystal was a randomized, openlabel, phase 3 rct that randomised patients to cetuximab plus folfiri n599, given once weekly or to folfiri alone n599. Fire 3 was a randomised phase 3 trial comparing folfiri plus cetuximab with folfiri plus bevacizumab in the firstline treatment of patients with kras exon 2 wildtype metastatic colorectal cancer. Capitals indicate lifethreatening, underlines indicate most frequent. Infusionrelated effects severe infusionrelated effects rarely fatal reported in about 3 % of patients. Cetuximab and panitumumab are two distinct monoclonal antibodies mabs targeting the epidermal growth factor receptor egfr, and both are widely used in combination with chemotherapy or as monotherapy to treat patients with ras wildtype metastatic colorectal cancer.
Relation of cetuximabinduced skin toxicity and early. Crystalcetuximab combined with irinotecan in firstline therapy for metastatic colorectal cancer. Folfiri plus cetuximab versus folfiri plus bevacizumab as firstline treatment for patients with metastatic colorectal cancer fire 3. Final recommendation for cetuximab erbitux for metastatic colorectal cancer. Material and methods patient population and treatment study design. The folfiri plus cetuximab versus folfiri plus bevacizumab as firstline treatment for patients with metastatic colorectal cancer fire 3 trial was a randomized phase 3 trial comparing firstline folfiri plus cetuximab vs folfiri plus bevacizumab in patients with kras wt mcrc. Effect of firstline chemotherapy combined with cetuximab or. The fire 3 study aio krk0306 was initiated as a randomized multicenter trial to compare the efficacy of folfiri plus cetuximab cet to folfiri plus bevacizumab bev as firstline treatment in mcrc patients. The fire 3 trial was an openlabel randomized prospective multicenter phase iii trial comparing the effectiveness of fluorouracil, folinic acid and irinotecan folfiri plus cetuximab to folfiri plus bevacizumab as firstline therapy in patients with kras exon 2 codon 12 wildtype mcrc. Fire 3 find, read and cite all the research you need on researchgate. Analysis of krasnras and braf mutations in fire 3 a randomized phase iii study of folfiri plus cetuximab or bevacizumab as first line treatment for wild type kras exon 2 metastatic colorectal cancer patients. Publications home of jama and the specialty journals of. Purpose we investigated choice and efficacy of subsequent treatment, with special focus on secondline therapy, in the fire 3 trial folfiri plus cetuximab arm a or bevacizumab arm b for patients with kras wildtype metastatic colorectal cancer.
An ecog performance status of 01 was present in 98% of patients, 66% were male, and their median age was 64 years. This is the first head to head comparison of cetuximab versus bevacizumab in firstline treatment of mcrc. Request pdf folfiri plus cetuximab versus folfiri plus bevacizumab for metastatic colorectal cancer fire3. Schrag d, chung ky, flombaum c, saltz l cetuximab therapy and symptomatic hypomagnesemia. Publications home of jama and the specialty journals of the.
Role of ccl5 and ccr5 gene polymorphisms in egfr signaling. Crystal randomized patients to cetuximab plusfolfiri irinotecan, leucovorin, fluorouracil or to folfiri alone fire 3 randomised patients to cetuximab plus folfiri or bevacizumab plus folfiri. Highlights of prescribing information these highlights do not. Folfiri plus cetuximab versus folfiri plus bevacizumab as firstline treatment for patients with metastatic colorectal cancer fire3. Medlineplus information on cetuximab a lay language summary of important information about this drug that may include the following.
Costeffectiveness of cetuximab as firstline treatment. Folfiri plus cetuximab versus folfiri plus bevacizumab for metastatic colorectal cancer fire3. The secondline treatment table 1 and firstline treatment ae risks table 2 were also derived from fire 3 data. Fire3 used the proportion of patients who achieved an objective response to treatment as its primary endpoint and there was no significant. Patients receiving off protocol docetaxel plus cetuximab every other week had a median os of 8.
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. Cetuximab is an epidermal growth factor receptor binding fab. Relevance of liverlimited disease in metastatic colorectal cancer. Closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after erbitux administration. Impact of subsequent therapies on outcome of the fire3aio. Serious infusion reactions and cardiopulmonary arrest infusion reactions.
Genomic dna was extracted from 491 samples of two different cohorts with kras wildtype mcrc from the fire 3 trial. Three studies, the phase iii fire 3 aio krk0306, the phase ii peak, and the recently presented phase iii calgbswog 80405 trial, have addressed this issue faceon, directly comparing the addition of bevacizumab versus cetuximab or panitumumab to folfoxfolfiri in terms of. Single nucleotide polymorphisms snps of ccl5 and ccr5 genes were analyzed by pcrbased direct sequencing. First, the fire3 trial n592 led by the arbeitsgemeinschaft internistische onkologie.
Serious infusion reactions occurred with the administration of erbitux in approximately 3 % of patients in clinical trials, with fatal outcome reported in less than 1 in. Go to the crystal, fire 3, and calgbswog 80405 data. In the fire 3 folfiribevacizumab cohort, bevacizumab was given at a dose of 5 mgkg biweekly. The fire 3 study aio krk0306 was initiated as a randomized multicenter trial to compare the efficacy of folfiri plus cetuximab cet to folfiri we use cookies to enhance your experience on our website. Planned accrual is 284 evaluable patients per treatment arm. Fire 3 was a prospective, multicenter, openlabel phase iii study nct00433927, the design of which has been described elsewhere. By continuing to use our website, you are agreeing to our use of cookies. Severe grades 3 and 4 infusion reactions occurred in 2. Sep 20, 2019 the only randomized, phase 3 trial to compare cetuximab and panitumumab directly was aspecct, which confirmed the noninferiority of panitumumab compared with cetuximab as a monotherapy in the third and laterline setting in patients with kras wt mcrc. Cetuximab or bevacizumab with firstline chemotherapy in. A randomized phase iii study of folfiri plus cetuximab or bevacizumab as firstline treatment for wildtype kras exon 2.
Cetuximab vs bevacizumab combined with either mfolfox6 or folfiri chemotherapy regimen chosen. These outcomes might partly account for the overall survival advantage of folfiri plus cetuximab seen in the fire3 trial. The fire 3 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. Objective response rate the primary end point and pfs were. Fire3 randomised patients to cetuximab plus folfiri or bevacizumab plus. Cea response is associated with tumor response and. Complete erbitux administration 1 hour prior to irinotecan, platinumbased therapy with fluorouracil or folfiri.
Firstline therapy with folfiri plus cetuximab or bevacizumab in patients with kras wildtype tumors in metastatic colorectal cancer dominik p. Cetuximab continuation after first progression in metastatic. Patients were initially recruited without regard to. Impact of subsequent therapies on outcome of the fire3. The primary study endpoint is objective response rate. The primary endpoint of the fire 3 study was the proportion of patients achieving an objective response according to response evaluation criteria in solid tumors recist 1. Sep 15, 2015 three studies, the phase iii fire 3 aio krk0306, the phase ii peak, and the recently presented phase iii calgbswog 80405 trial, have addressed this issue faceon, directly comparing the addition of bevacizumab versus cetuximab or panitumumab to folfoxfolfiri in terms of efficacy outcomes. Cetuximab erbitux for metastatic colorectal cancer. Full prescribing information erbitux cetuximab warning. Firstline treatment of metastatic colorectal cancer. Folfiri plus cet as firstline treatment of kras wt mcrc patients resulted in comparable overall response rates orr and progression free survival pfs when compared to. Pdf folfiri plus cetuximab versus folfiri plus bevacizumab as. Definition from the nci drug dictionary detailed scientific definition and other names for this drug.
The primary end point was the overall response rate orr. Signs and symptoms included rapid onset of airway obstruction bronchospasm, stridor, hoarseness, hypotension, shock,loss of consciousness, myocardial infarction, andor cardiac arrest. Although often considered interchangeable, the two antibodies have different molecular structures and can behave. Volker heinemann, clinical center of munich university lmu protocol committee. Folfiri plus cetuximab versus folfiri plus bevacizumab as. Distinguishing features of cetuximab and panitumumab in. Cetuximab is also being studied in the treatment of other types of cancer. Optimising the use of cetuximab in the continuum of care for. Folfiri plus cetuximab versus folfiri plus bevacizumab for. The primary endpoint of the fire 3 study was the proportion of patients achieving an objective response according to response evaluation. Request pdf on dec 1, 2014, fausto petrelli and others published folfiri with cetuximab or bevacizumab. A polymorphism within the vitamin d transporter gene. The fire 3 aio krk0306 study design, treatment parameters, and eligibility criteria have been reported previously.
The fire 3 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. Optimising the use of cetuximab in the continuum of care. Administer 400 mgm 2 initial dose as a 120minute intravenous infusion followed by 250 mgm 2 weekly infused over 60 minutes. Pdf the aio krk0306 trial compares the efficacy of infusional. Receipt of secondline therapy was based on fire 3 table 1 and secondline treatment duration of 7 cycles was based on published literature. Patients were initially recruited without regard to kras tumour mutation status.
Pd027braf mutant and ras mutant patients treated with. Fire 3 randomized 592 patients with wildtype tumors to folfiri every 2 weeks plus cetuximab 400 mgm2 on day 1, followed by 250 mgm2 weekly, or bevacizumab 5 mgkg every 2 weeks. Quality of life analysis in patients with ras wildtype metastatic. Clinical study protocol aio crc 0306fire 3 randomized study to investigate the efficacy of folfiri in combination with cetuximab vs. Results of the ras wt subset of the aspecct study are still pending. Folfiri plus cetuximab versus folfiri plus bevacizumab for metastatic colorectal cancer fire 3. Folfiri plus cetuximab vs folfiri plus bevacizumab. The fire 3 phase iii clinical trial demonstrated the marked advantage of prolonging the median overall survival of patients with final ras wildtype wt leftsided metastatic colorectal cancer mcrc by 38. Costeffectiveness analysis of firstline folfiri combined. Cea response is associated with tumor response and survival. Oncology group 80405 trial 7 and fire3 folfiri plus cetuximab vs. Cetuximab plus chemotherapy is a firstline treatment option in metastatic. The fire3 trial is a multicenter randomized phase iii trial investigating 5fu, folinic acid and irinotecan folfiri plus cetuximab versus folfiri plus. Patients and methods start of subsequentline second or third therapy was defined as use of an antitumor drug that was not part of the previous.
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