title: Symptom and quality of life benefit of afatinib in advanced non-small-cell lung cancer patients previously treated with erlotinib or gefitinib: results of a randomized phase IIb/III trial (LUX-Lung 1).
abstract: BACKGROUND
  Patient-reported symptom and health-related quality of life (HRQoL) benefit of afatinib, a novel, irreversible, ErbB Family Blocker, was investigated in a double-blind, randomized, phase IIb/III trial (LUX-Lung 1).
  
  
  METHODS
  Five hundred and eighty-five patients with lung adenocarcinoma (stage IIIb/IV), who had progressed after chemotherapy (1-2 lines) and at least 12 weeks of erlotinib or gefitinib, were randomized (2:1) to receive either afatinib plus best supportive care (BSC) or placebo plus BSC. Symptom and HRQoL benefit were measured using the lung cancer-specific European Organisation for Research and Treatment of Cancer (QLQ-C30/LC13) and EuroQol (EQ-5D) questionnaires. Non-small-cell lung cancer-related symptoms (cough, dyspnea, and pain) were prespecified using three preplanned analyses (percentage of patients improved/worsened/stable, change in scores over time, and time to deterioration of scores).
  
  
  RESULTS
  Compared with patients on placebo, a significantly higher proportion of afatinib-treated patients showed an improvement in cough (p < 0.0001), dyspnea (p = 0.006), and pain (p < 0.0001). Afatinib also significantly improved the mean scores over time for cough (p < 0.0001), dyspnea (p = 0.0161), and pain (p = 0.0056); significantly delayed the time to deterioration for cough (p < 0.001); and showed a trend in delaying dyspnea (p = 0.170) and pain (p = 0.287). Consistent with the adverse-event profile of afatinib, a significantly (p < 0.05) higher proportion of afatinib-treated patients showed worsening of diarrhea, sore mouth, dysphagia, and appetite scores. However, compared with placebo, afatinib significantly (p < 0.05) improved QoL assessed with the EQ-5D questionnaire and global health status/QoL, physical functioning, and fatigue, which were assessed with the European Organisation for Research and Treatment of Cancer questionnaires.
  
  
  CONCLUSIONS
  In the LUX-Lung 1 trial, the addition of afatinib to BSC significantly improved non-small-cell lung cancer-related symptoms (cough, dyspnea, and pain), fatigue, physical functioning, and HRQoL and significantly delayed time to deterioration of cough.
authors: McGill University Health Center, Montreal, Canada. hirsh@muhc.mcgill.ca
authors: Vera
authors: V
authors: Hirsh
authors: Jacques
authors: J
authors: Cadranel
authors: Xiuyu Julie
authors: XJ
authors: Cong
authors: Diane
authors: D
authors: Fairclough
authors: Henrik W
authors: HW
authors: Finnern
authors: Robert M
authors: RM
authors: Lorence
authors: Vince A
authors: VA
authors: Miller
authors: Michael
authors: M
authors: Palmer
authors: James Chih-Hsin
authors: JC
authors: Yang
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D000077716:Afatinib; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D003371:Cough / Q000139:chemically induced / Q000517:prevention & control; D004311:Double-Blind Method; D004417:Dyspnea / Q000139:chemically induced / Q000517:prevention & control*; D000069347:Erlotinib Hydrochloride; D005221:Fatigue / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D000077156:Gefitinib; D006801:Humans; D008137:Longitudinal Studies; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D011379:Prognosis; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use*; D016879:Salvage Therapy
chemical_list: D011799:Quinazolines; D000077716:Afatinib; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib