title: Correlation between development of rash and efficacy in patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in two large phase III studies.
abstract: OBJECTIVE
  Data from two large phase III studies were analyzed to characterize the correlation between the occurrence of rash during treatment with the epidermal growth factor receptor inhibitor erlotinib and improved clinical outcomes.
  
  
  METHODS
  Overall survival, progression-free survival (PFS), and tumor response were compared between patients in a rash-evaluable subset who did or did not develop rash in National Cancer Institute of Canada Clinical Trials Group Studies BR.21 (single agent in non-small-cell lung cancer, n = 444 in erlotinib group and n = 229 in placebo group) and PA.3 (combination with gemcitabine in pancreatic cancer, n = 254 in erlotinib plus gemcitabine group and n = 245 in placebo plus gemcitabine group).
  
  
  RESULTS
  Presence of rash strongly correlated with overall survival in both studies. In Study BR.21, these correlations increased with rash severity grade: grade 1 versus no rash [hazard ratio (HR), 0.41, P < 0.001] and grade >or=2 versus no rash (HR, 0.29, P < 0.001). Similar results were observed for PFS. Disease control (complete response + partial response + stable disease) seemed to increase with the presence and severity of rash. In Study PA.3, grade >or=2 rash (but not grade 1) strongly correlated with overall survival improvement: grade >or=2 versus no rash (HR, 0.47, P < 0.001). Similarly, grade >or=2 rash was strongly correlated with improvements in PFS and disease control.
  
  
  CONCLUSIONS
  Physicians and patients should view rash development as a positive event indicative of greater likelihood of clinical benefit. Further studies are required to identify patients most likely to develop rash and to determine if dose escalation to induce rash can improve efficacy.
authors.affiliation: OSI Pharmaceuticals, Boulder, Colorado 80301, USA. bwacker@osip.com
authors.forename: Bret
authors.initials: B
authors.lastname: Wacker
authors.forename: Tina
authors.initials: T
authors.lastname: Nagrani
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Weinberg
authors.forename: Karsten
authors.initials: K
authors.lastname: Witt
authors.forename: Gary
authors.initials: G
authors.lastname: Clark
authors.forename: Pablo J
authors.initials: PJ
authors.lastname: Cagnoni
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D005076:Exanthema / Q000139:chemically induced*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000093542:Gemcitabine