title: Skin toxicity and quality of life during treatment with panitumumab for RAS wild-type metastatic colorectal carcinoma: results from three randomised clinical trials.
abstract: Epidermal growth factor receptor inhibitors such as panitumumab are associated with characteristic skin toxicities. We summarise data from three panitumumab clinical trials to investigate the potential impact of skin toxicity on quality of life (QoL) in patients with metastatic colorectal cancer (mCRC).
  
  
  
  The studies were randomised, open-label trials comparing standard treatment (first-line FOLFOX4 [n = 456], second-line FOLFIRI [n = 381], or best supportive care [n = 114]) with or without panitumumab in adults with KRAS/NRAS (RAS) wild-type mCRC. QoL was assessed using the EuroQoL 5-domain health state index (HSI) and overall health rating (OHR) measures. Impact of skin toxicity on changes in QoL scores was estimated using a linear mixed-effects model. Worst skin toxicity was defined in separate models as a subgroup variable or as a measure over time.
  
  
  
  Regardless of analysis method, there were no statistically significant differences between the panitumumab and comparator arms in any of the studies in terms of change in HSI or OHR scores. There were no statistically significant differences in QoL outcomes between patients with worst skin toxicity grade <3 and those with grade ≥3. In addition, there were no statistically significant differences between the panitumumab and comparator arms in subgroups of patients with worst skin toxicity of grade <3 and ≥3.
  
  
  
  Addition of panitumumab to chemotherapy in RAS wild-type mCRC has no statistically significant negative effect on overall QoL, despite skin toxicity. Skin toxicity of worst grade ≥3 appeared to have similar impact on QoL as skin toxicity of grade <3.
authors.affiliation: Biostatistics, Amgen Ltd, 1 Uxbridge Business Park, Sanderson Road, Uxbridge, Middlesex, UB8 1DH, UK. reijak@amgen.com.
authors.forename: Reija
authors.initials: R
authors.lastname: Koukakis
authors.affiliation: Global Health Economics, Amgen (Europe) GmbH, Zug, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gatta
authors.affiliation: Global Health Economics, Amgen (Europe) GmbH, Zug, Switzerland.
authors.forename: Guy
authors.initials: G
authors.lastname: Hechmati
authors.affiliation: Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy.|Università degli Studi di Milano, Milan, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Siena
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000077544:Panitumumab; D011788:Quality of Life / Q000523:psychology*; D012871:Skin Diseases / Q000209:etiology* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000077544:Panitumumab
keywords: Colorectal cancer; Epidermal growth factor receptor inhibitors; Panitumumab; Quality of life; Skin toxicity