title: Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy.
abstract: BACKGROUND
  The authors explored the association of skin toxicity (ST) severity as measured by patient-reported ST and Common Terminology Criteria for Adverse Events (CTCAE) grading with efficacy of panitumumab, a fully human antiepidermal growth factor receptor antibody, from a phase 3 metastatic colorectal cancer (CRC) trial.
  
  
  METHODS
  Patients were randomized to panitumumab plus best supportive care (BSC) vs BSC alone. ST by modified National Cancer Institute CTCAE v3.0 and modified Dermatology Life Quality Index (mDLQI), health-related quality of life (HRQOL), and CRC symptoms were measured. ST was analyzed using a landmark approach. Associations by KRAS mutational status were also assessed.
  
  
  RESULTS
  Of 463 patients, 208 of 231 (90%) panitumumab patients and 184 of 232 (79%) BSC patients had > or = 1 postbaseline patient-reported outcome (PRO) assessment. Panitumumab patients with more severe ST had significantly longer overall survival (OS) (grade 2-4:grade 1; hazard ratio, 0.60; P = .0033). Lower mDLQI scores (< 67; more bothersome ST) were associated with longer OS (Cox model, P < .0001). Similar results were observed with progression-free survival (PFS). An inverse relation between mDLQI and HRQOL scores was observed, suggesting that ST bother correlated with better HRQOL. KRAS and PRO data were available in 363 patients (188 panitumumab; 175 BSC). Longer OS was associated with lower mDLQI scores, regardless of KRAS status. Longer PFS was associated with more severe ST (lower mDLQI scores and higher CTCAE grade ST) in patients with wild-type (WT) KRAS tumors, but not in patients with mutant KRAS tumors.
  
  
  CONCLUSIONS
  More severe ST, by both clinical grading and PRO, is associated with better CRC symptoms and HRQOL and with longer OS and PFS among panitumumab-treated patients. The associations for PFS were more pronounced in patients with WT KRAS tumors.
authors.affiliation: Department of HepatoGastroenterology, Digestive Oncology Unit, Ghent University Hospital, Ghent, Belgium. marc.peeters@ugent.be
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: Alberto
authors.initials: A
authors.lastname: Sobrero
authors.forename: Alain
authors.initials: A
authors.lastname: Hendlisz
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
authors.forename: Haralabos
authors.initials: H
authors.lastname: Kalofonos
authors.forename: Giovanna
authors.initials: G
authors.lastname: Devercelli
authors.forename: Michael
authors.initials: M
authors.lastname: Wolf
authors.forename: Rafael G
authors.initials: RG
authors.lastname: Amado
mesh_terms: D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000276:immunology; D011905:Genes, ras; D006801:Humans; D009154:Mutation; D000077544:Panitumumab; D011788:Quality of Life; D012871:Skin Diseases / Q000139:chemically induced*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000077544:Panitumumab; D066246:ErbB Receptors