Research Paper Volume 12, Issue 8 pp 7129—7162

Therapeutic options for advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer: a Bayesian network secondary analysis

Xinmin Zeng 1, , Xuan Wan 2, , Jun Xu 3, , Hui Wang 1, , Hua Chen 1, , Qinghua Zeng 2, , Wenxiong Zhang 4, , Binghao Zhao 5, ,

  • 1 Department of Thoracic Surgery, Nanchang First Hospital, Nanchang 330008, China
  • 2 Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
  • 3 Department of Oncology, Nanchang First Hospital, Nanchang 330008, China
  • 4 Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China
  • 5 Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China

received: November 2, 2019 ; accepted: March 29, 2020 ; published: April 23, 2020 ;
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Copyright © 2020 Zeng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The most favorable treatments for advanced EGFR-mutant NSCLC are less indicated. Forty-one studies were eligible for this Bayesian network secondary analysis. For PFS, erlotinib (Erlo)+bevacizumab (Bev) (HR 0.26, 95% CrI: 0.08-0.75 vs placebo), osimertinib (Osi) (HR 0.29, 0.11-0.70 vs placebo), and afatinib (Afa) were top-ranking individual treatments, while immunotherapy (IT)+anti-VEGFR (aVEGFR)+platinum-based therapy (Plat) (HR 0.42, 0.06-2.63 vs placebo), EGFR-TKI (ET)+aVEGFR (HR 0.35, 0.14-0.85 vs placebo), and ET+aVEGFR+Plat were top-ranking medication classes. For OS, Osi (HR 0.52, 0.10-2.00 vs placebo), cetuximab (Cet)+Bev+Plat (HR 0.51, 0.06-3.38 vs placebo), and cilengitide (Cil)+Cet+Plat were top-ranking individual treatments, while ET+aVEGFR+Plat, ET+Plat, and third-generation EGFR-TKI (3rd ET) were top-ranking medication classes. For PFS regarding the EGFR genomic aberration status, Erlo+Bev, Osi, and Afa were superior for exon 19 deletion status, whereas ET+Bev, Osi, and gefitinib (Gef)+pemetrexed (Peme) were excellent for exon 21 L858Arg mutation status. The results were consistent in terms of the ORR and DoR and remained robust across sensitivity analyses. However, Erlo + Bev had the most grade 3 or higher adverse events. Osi, Erlo+Bev, and Erlo+Bev+Plat are reasonably recommended to balance PFS and OS, but adverse events should be considered. IT+aVEGFR+Plat shows potential superiority, but more clinical evidence is needed.


EGFR: epidermal growth factor receptor; EGFR-TKI: epidermal growth factor receptor-tyrosine kinase inhibitor; NSCLC: non-small cell lung cancer; RCT: randomized controlled trials; PFS: progression-free survival; OS: overall survival; ORR: objective response rate; DoR: duration of response; NMAs: network meta-analyses; HR: hazard ratio; OR: odd ratio; MD: mean difference; CrI: credible interval; SD: standard deviation; Gef: gefitinib; Erlo: erlotinib; Ico: icotinib; Afa: afatinib; Dac: dacomitinib; Osi: osimertinib; Naq: naquotinib; Bev: bevacizumab; Ona: onartuzumab; Tiv: tivantinib; Sun: sunitinib; Peme: pemetrexed; Cil: cilengitide; Cet: cetuximab; Plat: platinum-based therapy; Mot: motesanib; Doc: docetaxel; Vin: vinorelbine; WBRT: whole-brain radiotherapy; ET: EGFR-TKI; VEGF: vascular endothelial growth factor; VEGFR: vascular endothelial growth factor receptor; MT: MET-TKI; CT: cytotoxic therapy; 19 del: exon 19 deletion; 21 L858R: 21 L858Arg mutation; ESMO: the European Society for Medical Oncology; ASCO: the American Society of Clinical Oncology; FDA: food and drug administration; NCCN: National Comprehensive Cancer Network; DIC: deviance information criteria; MCMC: The Markov Chain Monte Carlo; CNS: central nervous system; PD-L1: the programmed cell death-ligand 1; TMB: tumor mutational burden; AEs: adverse events.