1263P - Impact of epidermal growth factor receptor-tyrosine kinase inhibitor treatment in advanced non-small cell lung cancer: a meta-analysis

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Cytotoxic agents
Non-small-cell lung cancer
Biological therapy
Presenter Chee Khoon Lee
Authors C.K. Lee1, C. Brown2, R. Gralla3, V. Hirsh4, A. Inoue5, V. Gebski6, J. Yang7
  • 1Nhmrc Clinical Trials Centre, University of Sydney, 2050 - Sydney/AU
  • 2Clinical Trials, NHMRC Clinical Trials Centre, University of Sydney, Sydney/AU
  • 3Department Of Medicine, Hofstra University School of Medicine, New York/US
  • 4Oncology, McGill University Health Centre, H3A 1A1 - Montreal/CA
  • 5Department Of Respiratory Medicine, Tohoku University, JP-980-8575 - Sendai/JP
  • 6Biostatistics And Research Methodology, NHMRC Clinical Trials Centre, University of Sydney, 2050 - Sydney/AU
  • 7Department Of Oncology, National Taiwan University Hospital, TW-100 - Taipei/TW



Previous meta-analyses have reported that epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) improves progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) harbouring EGFR mutation. We examined the influence of EGFR-TKI on PFS and overall survival (OS) in those with (EGFR+) and without mutation (EGFR-).


We included published and unpublished randomised trials of advanced NSCLC that compared EGFR-TKI monotherapy or combination EGFR-TKI chemotherapy with chemotherapy or placebo. We used published hazard ratios (HR) if available, or derived treatment estimates from other survival data. We investigated treatment effects in different treatment settings and trial regimens.


We identified 20 eligible trials investigating EGFR-TKI in front-line (n = 12), second or subsequent (n = 5), and maintenance (n = 3) treatment, with EGFR status known in 3198 (23%) patients. Overall, HR for EGFR-TKI over control for PFS were (EGFR+) 0.37 (95% CI, 0.32 to 0.42; p < 0.001) and (EGFR-) 1.02 (95% CI, 0.93 to 1.12; p = 0.67). EGFR mutation is predictive of PFS benefit with EGFR-TKI in all settings: front-line HR (EGFR+) 0.39, p < 0.005, HR (EGFR-) 1.07, p = 0.27, interaction p < 0.001; second or subsequent lines HR (EGFR+) 0.38, p = 0.01, HR (EGFR-) 1.22, p = 0.07, interaction P = 0.003; maintenance HR (EGFR+) 0.15, p < 0.001, HR (EGFR-) 0.81, p = 0.02, interaction p = 0.02. There was no difference in OS for patients treated with EGFR-TKI or control in these subgroups of patients: HR (EGFR+) 0.95, p = 0.21; HR (EGFR-) 0.95; p = 0.29.


In this meta-analysis, treatment with EGFR-TKI was found to significantly delay disease progression in EGFR+ patients; however, no impact on OS was identified. EGFR mutation is a predictive biomarker of PFS benefit with EGFR-TKI treatment in all settings. These findings support assessment for EGFR mutation before initiation of EGFR-TKI treatment and that EGFR-TKI should be considered as front-line therapy in EGFR+ patients with advanced NSCLC.


R. Gralla: Consultant or advisory role for Boehringer Ingelheim.

V. Hirsh: Advisory role for Boehringer Ingelheim.

A. Inoue: Received lecture fees and research grants from AstraZeneca.

C.J. Yang: Advisory roles for Boehringer Ingelheim, AstraZeneca, Roche and OSI, and have received honoraria from AstraZeneca, Roche and OSI.

All other authors have declared no conflicts of interest.