title: Is progression-free survival associated with a better health-related quality of life in patients with lung cancer? Evidence from two randomised trials with afatinib.
abstract: OBJECTIVE
  Progression-free survival (PFS) is frequently used as an efficacy end point in oncology clinical trials. However, there is limited evidence to support a positive association between improvement in PFS and improvement in health-related quality of life (HRQoL). The association between PFS and HRQoL was evaluated in two randomised trials.
  
  
  METHODS
  Data from two randomised controlled trials in patients with non-small cell lung cancer (NSCLC; LUX-Lung 1 and LUX-Lung 3) were used to investigate HRQoL in patients to determine whether tumour progression is accompanied by worsening HRQoL. HRQoL was assessed using the cancer-specific European Organization for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30, the EuroQol EQ-5D overall utility and EuroQol EQ visual analogue scale. In both studies, progression was evaluated by independent review using RECIST criteria (primary end point) and also by investigator assessment. The relationship between tumour progression and HRQoL was evaluated using analysis of covariance and a longitudinal model.
  
  
  RESULTS
  Compliance with HRQoL questionnaire completion was high. In both studies, patients with progression consistently experienced numerically poorer HRQoL at the time of progression than patients without progression. Differences in mean scores were statistically significant (p<0.05) between patients with and without progression at week 4 in all analyses in LUX-Lung 1 and at multiple time points in LUX-Lung 3. Results from the longitudinal analysis showed that progression (by independent review and investigator assessment) appears to have consistent negative impact on all three HRQoL measures (all p<0.0001).
  
  
  CONCLUSIONS
  Tumour progression in patients with NSCLC was associated with statistically significant worsening in HRQoL. These findings confirm the value of PFS as a patient-relevant end point.
authors.affiliation: Boehringer Ingelheim GmbH, Ingelheim, Germany.
authors.forename: Ingolf
authors.initials: I
authors.lastname: Griebsch
authors.affiliation: Keele University, Keele, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Palmer
authors.affiliation: Institute of Applied Health Sciences, University of Aberdeen, Scotland, UK.|Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Fayers
authors.affiliation: Independent Statistical Consultant, Cheshire, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Ellis
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000077716:Afatinib; D018572:Disease-Free Survival; D006304:Health Status; D006801:Humans; D008137:Longitudinal Studies; D008175:Lung Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011788:Quality of Life; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D000077716:Afatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: ONCOLOGY