Symptom Response in NSCLC Patients Treated with Erlotinib: QOL Analysis of the NCIC CTG BR.21 Trial

Reviewer: S. Jack Wei, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 17, 2005

Presenter: A. Bezjak
Presenter's Affiliation: National Cancer Institute  Canada
Type of Session: Scientific


  • The NCIC CTG BR.21 trial was a randomized phase III trial of Erlotinib (Tarceva) and placebo as second-line therapy for patients with advanced non-small cell lung cancer (NSCLC).
  • 731 previously treated patients who had received 1 or 2 other chemotherapy regimens were randomized in a 2:1 randomization scheme to:
    1. Erlotinib (150 mg qd) until disease progression
    2. Placebo
  • 1-year overall survival (OS) favored the erlotinib group (31% vs. 22%, p<0.0001).
  • The initial analysis of this trial did not examine the quality of survival.
  • A quality of life (QOL) analysis was part of the original trial design and is reported here.

Materials and Methods

  • Validated QOL assessment tools including QLQ-C30 and Lung Cancer Module were utilized to assess global QOL, physical, role, emotional, social, cognitive functioning, and symptoms.
  • QOL assessment was performed at baseline and repeated at cycle 4, 7, 10, and 13 of erlotinib therapy.
  • The primary endpoint in the QOL was time to deterioration (10 point increase from baseline) of cough, dyspnea, and pain.


  • Compliance with QOL assessment was ~95% at baseline and ~65% in the erlotinib arm and ~75% in the placebo arm at cycle 13.
  • Time to deterioration for erlotinib vs. placebo:
    • Cough: 4.9 mo vs. 3.7 mo (p=0.04)
    • Dyspnea: 4.7 mo vs. 2.9 mo (p=0.04)
    • Pain: 2.8 mo vs. 1.9 mo (p=0.03)
  • Percentage of patients with improvement in QOL scores for erlotinib vs. placebo:
    • Global QOL: 35% vs. 26% (p<0.01)
    • Physical F: 31% vs. 19% (p<0.01)
    • Emotional F: 39% vs. 30% (p<0.01)
    • Role F: 39% vs. 32% (p=NS)
    • Social F: 39% vs. 37% (p=NS)
  • Percentage of patients with improvement in symptoms for erlotinib vs. placebo:
  • Pain: 42% vs. 28% (p=0.01)
  • Dyspnea: 34% vs. 23% (p=0.02)
  • Cough: 44% vs. 27% (p<0.01)
  • Fatigue: 48% vs. 38% (p=0.08)

Author's Conclusions

  • Erlotinib improved disease-free and overall survival in previously treated patients with NSCLC.
  • Erlotinib results in slower deterioration of disease-related symptoms compared to placebo.
  • QOL improved in more patients on the erlotinib arm compared to placebo.
  • These differences were clinically and statistically significant.

Clinical/Scientific Implications

The BR.21 trial is the first trial utilizing an inhibitor of epidermal growth factor receptor (EGFR) that has shown an overall survival benefit in patients with NSCLC.  For that reason alone, erlotinib is a reasonable therapeutic option as second-line therapy in patients with advanced NSCLC.  However, because it is being used in a palliative setting, QOL is an important component of assessing the utility of this treatment.  This report of the QOL of patients in the BR.21 trial shows improvement in several key QOL measures, a higher percent of patients experiencing improvement in cancer-related symptoms, and delay in progression of cancer-related symptoms for erlotinib over placebo.  This QOL analysis combined with the overall survival benefit makes erlotinib one of the primary therapy options a second-line therapy for advanced NSCLC.