title: Efficacy and Toxicity of Panitumumab After Progression on Cetuximab and Predictive Value of MiR-31-5p in Metastatic Wild-type KRAS Colorectal Cancer Patients.
abstract: In metastatic colorectal cancer (mCRC), panitumumab is generally considered to be ineffective after the progression on cetuximab therapy. However, few studies have demonstrated that a small subset of mCRC patients may benefit from panitumumab in this setting.
  
  
  
  In our study, wild-type KRAS mCRC patients, enrolled into the nationwide Czech registry CORECT between January 2007 and December 2012, were screened for panitumumab therapy after progression on cetuximab.
  
  
  
  We identified 26 mCRC in the registry with well documented progression on cetuximab in combination with irinotecan-based chemotherapy (FOLFIRI or irinotecan alone) who received panitumumab monotherapy. Partial response (PR) was achieved in 3 (11.5%) patients and stable disease (SD) in 7 (26.9%) patients after 8 weeks of therapy. Thirteen (50.0%) patients had evidence of progressive disease (PD) and in 3 (11.5%) cases response was not available. Furthermore, we confirmed that higher expression levels of newly described biomarker, miR-31-5p, in tumor are significantly associated with shorter progression-free survival (PFS) in patients treated with cetuximab (p=0.038); however, we did not observe association between miR-31-5p and response to panitumumab in mCRC patients after progression on cetuximab.
  
  
  
  It remains possible that a subset of mCRC patients may benefit from panitumumab after progression on cetuximab.
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic kiss@mou.cz on.slaby@gmail.com.
authors.forename: Igor
authors.initials: I
authors.lastname: Kiss
authors.affiliation: Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Jitka
authors.initials: J
authors.lastname: Mlcochova
authors.affiliation: Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Bortlicek
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Alexandr
authors.initials: A
authors.lastname: Poprach
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Drabek
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Vychytilova-Faltejskova
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Svoboda
authors.affiliation: Department of Oncology, Thomayer Hospital and Charles University First Faculty of Medicine, Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Buchler
authors.affiliation: Department of Oncology, Motol University Hospital and Charles University Second Faculty of Medicine, Prague, Czech Republic.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Batko
authors.affiliation: The Fingerland Department of Pathology, Charles University Medical Faculty Hospital, Hradec Kralove, Czech Republic.
authors.forename: Ales
authors.initials: A
authors.lastname: Ryska
authors.affiliation: Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic.
authors.forename: Marian
authors.initials: M
authors.lastname: Hajduch
authors.affiliation: Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic Central European Institute of Technology, Masaryk University, Brno, Czech Republic kiss@mou.cz on.slaby@gmail.com.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Slaby
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D000068818:Cetuximab / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D000077544:Panitumumab; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras); D000068818:Cetuximab
keywords: KRAS; Metastatic colorectal cancer; cetuximab; miR-31-5p; microRNA; panitumumab