title: Cetuximab plus irinotecan versus panitumumab in patients with refractory metastatic colorectal cancer in Ontario, Canada.
abstract: The addition of irinotecan to an epidermal growth factor receptor (EGFR) antibody has previously been shown to improve tumor response rate and time to progression but not overall survival (OS) for refractory metastatic colorectal cancer (mCRC). We assessed the "real-world" effectiveness and toxicity of the combination versus monotherapy. In Ontario, Canada, universal public funding is available for either cetuximab plus irinotecan (Cmab + I) combination therapy or panitumumab (Pmab) monotherapy, only in patients with refractory nonmutated RAS mCRC. All patients diagnosed before December 2012 and treated with an EGFR antibody for mCRC were identified from the Ontario drug database and linked to the Ontario Cancer Registry and other administrative databases to ascertain baseline characteristics, health services utilization, and outcomes. Multivariable Cox and logistic models were constructed to compare the time to treatment discontinuation (TTD), OS, emergency department (ED) or hospital visits between Cmab + I and Pmab. Observable confounders were adjusted for using propensity score methods. One thousand and eighty-one patients were identified (Cmab + I: 278, Pmab: 803). Patients receiving Cmab + I were younger (mean age 61 vs 64 years) and had a longer duration of prior irinotecan treatment. The use of Cmab + I as compared to Pmab alone was associated with a prolonged TTD [median: 3.8 months vs 2.8 months] and an improved OS [median: 8.8 months vs. 5.9 months] with an adjusted HR of 0.62 [95% CI 0.53-0.73, p < 0.001]. Both treatment regimens afforded similar 14-day mortality and incidence of ED or hospital visits. The findings for patients over and below the age of 65 were similar.
authors.affiliation: Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Katarzyna J
authors.identifier: 0000-0002-3995-0308
authors.initials: KJ
authors.lastname: Jerzak
authors.affiliation: Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Scott
authors.initials: S
authors.lastname: Berry
authors.affiliation: Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yoo-Joung
authors.initials: YJ
authors.lastname: Ko
authors.affiliation: Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.|Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada.|Cancer Care Ontario, Toronto, Ontario, Canada.
authors.forename: Craig
authors.initials: C
authors.lastname: Earle
authors.affiliation: Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Ontario, Canada.|Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.|Canadian Centre for Applied Research in Cancer Control, Toronto, Ontario, Canada.
authors.forename: Kelvin K W
authors.initials: KK
authors.lastname: Chan
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002170:Canada; D000068818:Cetuximab / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D000077544:Panitumumab; D000077146:Irinotecan; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab; D002166:Camptothecin
keywords: EGFR antibody; colorectal cancer; comparative effectiveness; elderly