Epidemiological and clinical burden of EGFR Exon 20 insertion in advanced non-small cell lung cancer: A systematic literature review

PLoS One. 2021 Mar 8;16(3):e0247620. doi: 10.1371/journal.pone.0247620. eCollection 2021.


Objectives: The burden of epidermal growth factor receptor (EGFR) exon 20 insertion mutation (Exon 20ins) in non-small cell lung cancer is not well understood. A systematic review was conducted to identify evidence on mutation frequency, prognostic impact, clinical, patient-reported, and economic outcomes associated with Exon 20ins.

Materials and methods: Searches were conducted in Embase and Medline and supplemented with recent conference proceedings. Included studies were not limited by intervention, geography, or publication year.

Results: Seventy-eight unique studies were included; 53 reporting mutation frequency, 13 prognostic impact, 36 clinical outcomes, and one humanistic burden. No economic burden data were identified. The frequency of Exon 20ins mutation ranged from 0.1% to 4% of all NSCLC cases and 1% to 12% of all EGFR mutations. Data on the prognostic impact of Exon 20ins were heterogeneous but highlighted poorer outcomes in patients with Exon 20ins mutation compared with patients with other EGFR mutations and EGFR wildtype across a wide range of therapies and treatment lines. Comparative evidence on the clinical efficacy and safety of currently available therapies were limited, as were sample sizes of studies reporting on real-world effectiveness. Nine single-arm trials and 27 observational studies reported clinical outcomes for patients with Exon 20ins. Trends towards better survival and response were observed for chemotherapy compared with TKIs as first-line treatments. For subsequent treatment lines, novel targeted therapies provided encouraging preliminary responses while results for chemotherapy were less favorable. Limited safety data were reported. One conference abstract described the symptom burden for Exon 20ins patients with fatigue and pain being most common.

Conclusion: Findings of the systematic review show a high unmet need for safe and efficacious treatments for patients with Exon 20ins as well and need for further evidence generation to better understand the patient-level and economic impact for these patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Americas / epidemiology
  • Antineoplastic Combined Chemotherapy Protocols*
  • Asia / epidemiology
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / epidemiology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Cohort Studies
  • ErbB Receptors / genetics
  • Europe / epidemiology
  • Exons
  • Gene Expression
  • Humans
  • Incidence
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / epidemiology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Mutagenesis, Insertional*
  • Mutation Rate
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use
  • Survival Analysis
  • Treatment Outcome


  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors

Grants and funding

Funding for this study was provided by Janssen Global Services, Raritan, NJ, US, wherein two of the coauthors are employees (TL and PM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.