title: Cetuximab plus irinotecan after irinotecan failure in elderly metastatic colorectal cancer patients: clinical outcome according to KRAS and BRAF mutational status.
abstract: BACKGROUND
  Scarce data are available about safety and efficacy of cetuximab in elderly metastatic colorectal cancer (mCRC) patients.
  
  
  METHODS
  We retrospectively analysed 54 irinotecan-refractory mCRC patients aged≥70 years treated with cetuximab plus irinotecan and evaluated clinical outcome according to KRAS and BRAF mutational status.
  
  
  RESULTS
  Median age was 73 years (70-82). Main grade 3-4 toxicities were skin rash (15%), diarrhea (19%) and neutropenia (13%). Irinotecan dose reduction was necessary in 39% of patients. Fifty-two (96%) patients were analysed for KRAS and BRAF status. The 29 KRAS wild-type patients achieved better RR (31% vs 4%; p=0.030) and median PFS (4.21 months vs 3.95 months; p=0.034; HR: 0.50, 95% CI: 0.27-0.95) when compared with KRAS mutated ones. RR (41% vs 3%; p=0.001) and mPFS (4.57 months vs 3.78 months, p=0.001; HR: 0.35, 95% CI: 0.19-0.66) were significantly higher among the 22 KRAS and BRAF wild-type patients compared to the 30 KRAS or BRAF mutated ones.
  
  
  CONCLUSIONS
  Cetuximab plus irinotecan has a favourable safety profile in elderly mCRC patients, but a reduced dose of irinotecan should be considered. Such a combination can be a useful option for elderly KRAS and BRAF wild-type patients.
authors.affiliation: U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Fornaro
authors.forename: Giacomo Giulio
authors.initials: GG
authors.lastname: Baldi
authors.forename: Gianluca
authors.initials: G
authors.lastname: Masi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Allegrini
authors.forename: Fotios
authors.initials: F
authors.lastname: Loupakis
authors.forename: Enrico
authors.initials: E
authors.lastname: Vasile
authors.forename: Samanta
authors.initials: S
authors.lastname: Cupini
authors.forename: Irene
authors.initials: I
authors.lastname: Stasi
authors.forename: Lisa
authors.initials: L
authors.lastname: Salvatore
authors.forename: Chiara
authors.initials: C
authors.lastname: Cremolini
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ruzzo
authors.forename: Emanuele
authors.initials: E
authors.lastname: Canestrari
authors.forename: Mauro
authors.initials: M
authors.lastname: Magnani
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D009154:Mutation / Q000235:genetics; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D017211:Treatment Failure; D018631:ras Proteins / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D000077146:Irinotecan; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002166:Camptothecin