Panitumumab, Anti-EGFR MoAb,Promising in Colon Cancer
This special “annual highlights” supplement to Oncology News International (ONI)is a compilation of selected news on important advances in the management ofgastrointestinal cancers over the past year, as reported in ONI. Guest Editor, Dr.James L. Abbruzzese, comments on the reports included herein and discussesdevelopments in the clinical management of GI cancers, with a look at the impactof targeted agents with cytotoxic chemotherapy, first-line and adjuvant therapies foradvanced disease, and the role of statins and COX-2 inhibitors in prevention.
NEW YORK-Panitumumab, a100% human high-affinity IgG2 monoclonalantibody (MoAb) against theepidermal growth factor receptor(EGFR), appears effective in the treatmentof colorectal cancer and is welltolerated, according to Joel RandolphHecht, MD, director of the GastrointestinalOncology Program,UCLA School of Medicine.Dr. Hecht presented recent clinicaldata on panitumumab in colorectalcancer at the Chemotherapy FoundationSymposium XXII. Panitumumab(formerly known as ABX-EGF, codevelopedby Amgen, Inc., and Abgenix)was created using Abgenix's Xeno-Mouse technology, which, accordingto the company, "enables the rapidgeneration and selection of high affinity,fully human antibody product candidatesto a variety of disease targets."Phase II MonotherapyDr. Hecht reviewed his group's ongoingmulticenter phase II trial of panitumumabmonotherapy, which he hadpresented at the 2004 ASCO annualmeeting (abstract 3511). In that study,the monoclonal antibody was foundto have antitumor activity when administeredas a single-agent to 148patients with metastatic colorectal cancerwho had failed to respond to chemotherapywith a fluoropyrimidinewith or without leucovorin, and irinotecan(Camptosar) or oxaliplatin(Eloxatin) or both.EGFR expression was determinedby immunohistochemistry. "I personallydo not think EGFR staining meansanything, but at the time the study wasdone, we thought it might be significant,"he added.Panitumumab was given at 2.5 mg/kg intravenously over 1 hour, once aweek for 8 weeks. "We've now gonebeyond this dosage, but that is howthis trial was done," Dr. Hecht commented.At least 95% of patients experiencedsome form of skin rash, butonly 3% had grade 3 rash, and nopatients had grade 4 rash. Grade 3fatigue and vomiting were seen in 2%and 1% of patients, respectively.Panitumumab was administeredwithout premedication, with the ex-ception of one patient who experienceda grade 3 infusion-related event."Response rates were very similarto what has been seen with cetuximab[Erbitux]," Dr. Hecht told ONI. "Theoverall response rate was 10%," with13 patients having responded at thetime of the first 8-week evaluation,and two patients responding after thesecond 8-week evaluation (both atweek 18). "There was also a reasonableamount of stable disease," he added,"but since 48% of patients wereeither responders or had stable diseaseat the first look, median time toprogression was only about 2 months."Median overall survival was 7.9months, and median time to progressionwas 2.0 months.Noting that some striking clinicalresponses were seen early in the courseof therapy, he added that "some ofthese patients responded clinicallywithin 1 week." As with trials of cetuximab,there was no correlation betweenthe degree of EGFR stainingand response to panitumumab, hesaid.Phase II With IFLDr. Hecht also discussed a phase IItrial of panitumumab with irinotecan,fluorouracil (5-FU), and leucovorin(IFL, Saltz regimen) in patients withmetastatic colorectal cancer, some resultsof which were presented at the29th ESMO (European Society forMedical Oncology) Congress by JordanBerlin, MD, of Vanderbilt UniversityMedical Center (abstract 265).The first part of this multicenter,open-label, single-arm study included19 patients who received first-linetherapy with panitumumab and standardIFL. Panitumumab 2.5 mg/kgwas administered over a 1-hour periodweekly in 6-week courses (on days1, 8, 15, 22, 29, and 36) immediatelyfollowed by irinotecan 125 mg/m2,leucovorin 20 mg/m2, and 5-FU500 mg/m2 on days 1, 8, 15, and 22.The second part is a trial of first-linetherapy with panitumumab/FOLFIRI(folinic acid [leucovorin], infusional5-FU, and irinotecan) in 24 patients.Data for the first part of the studyshowed an unacceptably high incidenceof diarrhea at 84% (grade 3 in42%) and a 16% incidence of nausea,abdominal pain, dehydration, and hypokalemia.Responses, assessed usingRECIST criteria, were comparable towhat has been seen in phase II studiesof IFL alone and of IFL with cetuximab,"with some stable disease and avery low incidence of progressive disease,"Dr. Hecht said.The overall response rate after6 weeks of therapy was 47% (42%partial response, 5% complete response),with stable disease in 32% ofpatients at week 6 or later. Medianprogression-free survival time was 8.2months.
