title: Quality of life during first-line FOLFOX4±panitumumab inRASwild-type metastatic colorectal carcinoma: results from a randomised controlled trial.
abstract: BACKGROUND
  Metastatic colorectal cancer is rarely curable. Improving quality of life is therefore a key treatment goal. We report quality of life for patients withRASwild-type metastatic colorectal cancer in the PRIME study.
  
  
  METHODS
  A randomised phase 3 open-label study of first-line panitumumab+FOLFOX4 vs FOLFOX4 enrolled adults with untreated metastatic colorectal cancer and an Eastern Cooperative Oncology Group performance status of 0-2. This analysis includes patients with wild-typeRAStumours (n=505). Quality of life (prespecified end point) was assessed using the EuroQoL 5-domain health state index and overall health rating in all patients and by early tumour shrinkage status (≥30% reduction in size by week 8; exploratory end point). Differences in quality of life were assessed using analysis of covariance and a mixed-effect piecewise linear model, and were also analysed by skin toxicity severity.
  
  
  RESULTS
  There were no statistically significant differences between treatment arms from baseline to progression or to discontinuation. Grade 3+ skin toxicity was reported by 38% of patients receiving panitumumab+FOLFOX4 and 2% receiving FOLFOX4 alone. There were no significant differences in quality of life between patients with grade 0-2 skin toxicity and those with grade 3+ skin toxicity. More patients receiving panitumumab+FOLFOX4 vs FOLFOX4 had early tumour shrinkage (p<.001). In patients with tumour symptoms at baseline, there were statistically significant improvements in quality of life in those with early tumour shrinkage versus those without early tumour shrinkage.
  
  
  CONCLUSIONS
  Addition of panitumumab to FOLFOX4 in first-line therapy for metastatic colorectal cancer prolongs survival and has no negative effect on overall quality of life compared with FOLFOX4 alone. Specific quality of life assessments for skin toxicity should be included in study designs to better define the direct effect of these adverse events.
  
  
  BACKGROUND
  NCT00364013.
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Oncology, Università degli Studi di Milano, Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
authors.affiliation: Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona , Barcelona , Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: Department of Oncology , Szent László Hospital , Budapest , Hungary.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Bodoky
authors.affiliation: Department of Medicine , Royal Marsden National Health Service Foundation Trust , London , UK.
authors.forename: David
authors.initials: D
authors.lastname: Cunningham
authors.affiliation: Department of Medical Oncology , Hospital Universitario Marqués de Valdecilla , Santander , Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivera
authors.affiliation: Faculty of Health Sciences , University of the Witwatersrand , Johannesburg , South Africa.
authors.forename: Paul
authors.initials: P
authors.lastname: Ruff
authors.affiliation: Service d'Oncologie-Hématologie , Grand Hôpital de Charleroi , Charleroi , Belgium.
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Canon
authors.affiliation: Department of Biostatistics , Amgen Ltd , Uxbridge , UK.
authors.forename: Reija
authors.initials: R
authors.lastname: Koukakis
authors.affiliation: Medical Development, Amgen (Europe) GmbH , Zug , Switzerland.
authors.forename: Gaston
authors.initials: G
authors.lastname: Demonty
authors.affiliation: Global Health Economics, Amgen (Europe) GmbH , Zug , Switzerland.
authors.forename: Guy
authors.initials: G
authors.lastname: Hechmati
authors.affiliation: Department of Medical Oncology , Institut de Cancérologie de l'Ouest (ICO) René Gauducheau , Nantes , France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
keywords: EGFR inhibitors; chemotherapy; metastatic colorectal cancer; quality of life; tumour shrinkage