Comparative outcome assessment of epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of advanced non-small-cell lung cancer: a network meta-analysis

Ramon Andrade De Mello _, Carles Escriu, Pedro Castelo-Branco, Paloma Lucena Cabral, Giannis Mountzios, Gilberto de Lima Lopes and Pedro Madureira

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Oncotarget. 2018; 9:11805-11815. https://doi.org/10.18632/oncotarget.23668

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Ramon Andrade De Mello1,2,3, Carles Escriu4,5, Pedro Castelo-Branco1,2,6, Paloma Lucena Cabral7, Giannis Mountzios8, Gilberto de Lima Lopes9 and Pedro Madureira10

1Division of Oncology, School of Medicine, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal

2Algarve Biomedical Center, Campus Gambelas, Faro, Portugal

3Research Centre/Department of Medical Oncology, Haroldo Juaçaba Hospital, Ceará Cancer Institute, Fortaleza, CE, Brazil

4Department of Medical Oncology, The Clatterbridge Cancer Centre NHS Foundation Trust, Warrington, Wirral and Liverpool, Merseyside, United Kingdom

5Cancer Research Centre, Department of Molecular and Clinical Cancer Medicine, The University of Liverpool, Liverpool, United Kingdom

6Centre for Biomedical Research, University of Algarve, Faro, Portugal

7Special Training Program (PET), Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil

8Department of Medical Oncology, University of Athens, Athens, Greece

9Sylvester Comprehensive Cancer Centre at the University of Miami, Miami, FL, USA

10Institute for Molecular and Cell Biology (IBMC) and Institute for Investigation and Innovation in Health (i3S), University of Porto, Porto, Portugal

Correspondence to:

Ramon Andrade De Mello, email: [email protected]

Keywords: non-small cell lung cancer; epidermal growth factor receptor; tyrosine kinase inhibitors

Received: June 20, 2017     Accepted: October 30, 2017     Published: December 23, 2017


Introduction: Tyrosine kinase inhibition of the epidermal growth factor receptor (EGFR) is the standard in the first line treatment of patients with advanced non-small–cell lung cancer (NSCLC) harbouring EGFR activating mutations. Here we aim to discern efficacy and toxicity measures through a meta-analysis of published studies that could aid treatment selection.

Materials And Methods: We performed a meta-analysis of the main randomized clinical trials evaluating the currently approved EGFR-TKIs in first-line of treatment of EGFR-positive advanced NSCLC. Cochrane guidelines were used for statistical analysis.

Results: 3,179 patients were included. All EGFR TKIs showed improved outcomes with respect to ORR and PFS when compared to standard platinum-doublet chemotherapy. Comparative ORR for gefitinib, erlotinib and afatinib were 52.1%, 67.3% and 61.6% respectively. HRs for PFS were 0.62 (95% CI, 0.38–1.00) for gefitinib, 0.28 (95% CI, 0.17–0.45) for erlotinib and 0.40 (95% CI, 0.20–0.83) for afatinib. HRs for OS were not statistically significant for any agent.

Conclusions: Our results suggest similar clinical efficacy and higher toxicity of Afatinib treatment. As this still remains the agent with best CSF penetration, we suggest its use is limited to patients presenting with brain metastasis. We suggest the use of Gefitinib in patients without CNS involvement. Faced with the impossibility to dose-reduce Gefitinib, Erlotinib represents a tolerable and effective alternative to Afatinib and Gefitinib if response to EGFR inhibition is considered still effective.

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